KR20140123777A - Genetic Marker for Diagnosis of Psoriasis and Method for diagnosis of Psoriasis using the same - Google Patents

Abstract

According to the present invention to provide information required for the diagnosis of psoriasis, provided is a method for measuring the expression level or the methylation level of one gene selected from the group consisting of a TP73 gene indicated by sequence number 9 of a base sequence from the biological sample of a subject, a FANK1 gene indicated by sequence number 10 of the base sequence, and a PPAPDC3 gene indicated by sequence number 11 of the base sequence. In addition, according to the present invention, provided are a composition and a kit for the diagnosis of psoriasis, which contain a formulation for measuring the expression level or the methylation level of a gene selected from the group consisting of a TP73 gene indicated by sequence number 9 of a base sequence, a FANK1 gene indicated by sequence number 10 of the base sequence, and a PPAPDC3 gene indicated by sequence number 11 of the base sequence. According to the present invention, the method and the composition are capable of providing the genetic information for the diagnosis of psoriasis, thereby effectively diagnosing the psoriasis.

Description

TECHNICAL FIELD The present invention relates to a genetic marker for psoriasis diagnosis and a diagnostic method for psoriasis using the same,

The present invention relates to a gene marker for psoriasis diagnosis and a method for diagnosing psoriasis using the same. More particularly, the present invention relates to (a) a TP73 gene represented by the nucleotide sequence of SEQ ID NO: 9 from the biological sample of the subject, Measuring the expression level or methylation level of any one gene selected from the group consisting of the FANK1 gene and the PPAPDC3 gene represented by the nucleotide sequence of SEQ ID NO: 11; And (b) comparing the expression level or the methylation level of the gene measured in the step (a) with an expression level or a methylation level of the same gene in a normal control sample, TP73 , FANK1, and PPAPDC3. The present invention also relates to a diagnostic kit and a kit for diagnosing psoriasis, which comprises an agent for measuring an expression level or a methylation level of a gene selected from the group consisting of FANK1 and PPAPDC3.

DNA methylation is one of the mechanisms that regulate gene expression by replacing the DNA sequence with the Methyl group, thereby lowering the reactivity of the DNA and increasing its stability. DNA is not methylated when first cloned, but becomes methylation after cloning. DNA methylation results in inactivation of the gene without variation in the DNA sequence, which is classified as epigenetic change, distinguishing it from genetic changes such as point mutations and genetic defects.

Recently, methods for diagnosing cancer through DNA methylation measurement have been proposed. DNA methylation occurs mainly in the cytosine of the CpG island (CpG island) of the promoter region of a specific gene, and thereby the binding of transcription factors is hindered And the methylation of the CpG island of the promoter of the tumor suppressor gene is highly useful for the cancer research. The methylation specific PCR (hereinafter referred to as "MSP ") or the automatic There have been active attempts to use such methods for the diagnosis and screening of cancer.

It is controversial whether methylation of promoter CpG is directly inducing carcinogenesis or secondary changes in carcinogenesis. However, in many cancers, tumor suppressor gene, DNA repair gene, And hypermethylation of regulatory genes have been shown to block the expression of these genes. In particular, it has been shown that hypermethylation occurs at the promoter region of a specific gene at an early stage of cancer development. Therefore, the promoter methylation of the tumor-associated gene has been recognized as an important index of cancer, and an attempt has been actively made to investigate the promoter methylation of tumor-associated genes in actual blood, sputum, saliva, stool, Cancer Res., 60: 892, 2000; Ahlquist, DA et al., Gastroenterol., ≪ RTI ID = 0.0 > 119: 1219,2000). However, the promoter methylation of genes related to other diseases has not been studied so far. In particular, gene promoters with specific methylation in psoriasis patients or their application studies have not been studied.

Psoriasis is a chronic inflammatory disease of the skin that is characterized by thick, scaly layers. Although the pathogenesis of psoriasis has not yet been clearly elucidated, cytokines released from T cells activated by various evidences have been reported to be T-cell mediated inflammatory diseases that promote keratinocytes proliferation (Prinz, JC et al., 1997 and Chang, JCC et al., 1994).

Studies have also shown that genetic factors are involved in the development of psoriasis. About one-third of patients have a family history, and the incidence of psoriasis in identical twins is three times higher than that of fraternal twins. In addition, the probability of psoriasis in the family is also in proportion to the relatedness (Wuepper et al., J. Invest. Dermatol., 95: 2S-4S 1990).

Currently, the treatment of psoriasis, such as temporarily relieving the symptoms of ointment or prescription to induce persistent skin care, is actually not fundamentally treated. Considering the side effects of psoriasis skin disease drugs including steroids, it is necessary to develop a method that can radically treat these diseases without adverse effects, and development of genetic targets and diagnostic methods therefor is needed.

Accordingly, the inventors of the present invention conducted a study on a novel method for the diagnosis of psoriasis. As a result, the present inventors completed the present invention by confirming that the methylation level of specific genes is significantly higher than that of the control group in which psoriasis patients are normal.

(A) a TP73 gene represented by the nucleotide sequence of SEQ ID NO: 9, a FANK1 gene represented by the nucleotide sequence of SEQ ID NO: 10, and a PPAPDC3 gene represented by the nucleotide sequence of SEQ ID NO: 11 from the biological sample of the subject Measuring an expression level or a methylation level of any one gene selected from the group consisting of And (b) comparing the expression level or the methylation level of the gene measured in step (a) with an expression level or methylation level of the same gene in a normal control sample. .

Another object of the present invention is to provide a method for screening for a mutant gene selected from the group consisting of the TP73 gene represented by the nucleotide sequence of SEQ ID NO: 9, the FANK1 gene represented by the nucleotide sequence of SEQ ID NO: 10, and the PPAPDC3 gene represented by the nucleotide sequence of SEQ ID NO: Of the gene of the present invention or a methylation level thereof.

Another object of the present invention is to provide a method for screening for a mutation in a gene selected from the group consisting of the TP73 gene represented by the nucleotide sequence of SEQ ID NO: 9, the FANK1 gene represented by the nucleotide sequence of SEQ ID NO: 10, and the PPAPDC3 gene represented by the nucleotide sequence of SEQ ID NO: A gene expression level or a methylation level in a subject's body.

(GenBank Accession No. NM_001126240), FANK1 (SEQ ID NO: 10 / GenBank Accession No. NM_145235), and PPAPDC3 (SEQ ID NO: 11) from a biological sample of a subject in order to achieve the above object. / GenBank Accession No. NM_032728), or a methylation level of a gene selected from the group consisting of: And (b) comparing the expression level or the methylation level of the gene measured in step (a) with an expression level or methylation level of the same gene in a normal control sample. to provide.

(GenBank Accession No. NM_001126240), FANK1 (SEQ ID NO: 10 / GenBank Accession No. NM_145235) and PPAPDC3 (SEQ ID NO: 11 / GenBank Accession No. NM_032728 ) Or an expression level or a methylation level of any one gene selected from the group consisting of < RTI ID = 0.0 > a < / RTI >

(GenBank Accession No. NM_001126240), FANK1 (SEQ ID NO: 10 / GenBank Accession No. NM_145235) and PPAPDC3 (SEQ ID NO: 11 / GenBank Accession No. NM_032728 ) Or an agent for measuring a gene expression level or a methylation level of a gene selected from the group consisting of: < RTI ID = 0.0 > a < / RTI >

Hereinafter, the present invention will be described in detail.

The present invention relates to a method of screening for (a) a polypeptide comprising the amino acid sequence of TP73 (SEQ ID NO: 9 / GenBank Accession No. NM_001126240), FANK1 (SEQ ID NO: 10 / GenBank Accession No. NM_145235) and PPAPDC3 (SEQ ID NO: 11 / GenBank Accession No. NM_032728) Measuring an expression level or a methylation level of any one gene selected from the group consisting of And (b) comparing the expression level or the methylation level of the gene measured in step (a) with an expression level or methylation level of the same gene in a normal control sample. to provide.

In the present invention, the expression level of the gene may be a method of measuring the mRNA or protein expression level of the gene, and more preferably the mRNA expression measurement.

For example, RT-PCR, competitive RT-PCR, real-time RT-PCR, and the like can be used to measure the expression level. , RNase protection assay (RPA), northern blotting, DNA microarray chip, Western blotting, enzyme-linked immunosorbent assay, radioimmunoassay (RIA) , One or more methods selected from the group consisting of radioimmunoprecipitation, Ouchteroni immunodiffusion, rocket immunoelectrophoresis, immunohistochemistry, immunoprecipitation, complement fixation, flow cytometry (FACS) and protein chips. And most preferably real-time RT-PCR.

The methylation of a gene results in inactivation of the gene without variation in the DNA sequence, which is classified as a postmenopausal change by distinguishing it from genetic changes such as point mutations and genetic defects. Changes in methylation levels include both hypermethylation and hypomethylation. Changes in the level of methylation are mainly studied in relation to cancer, and there is no known gene that specifically hypermethylated in CD ⁺ T cells associated with psoriasis.

Methods for measuring the methylation level include MIRA (methylated-CpG island recovery assay), PCR, methylation specific PCR, real time methylation specific PCR, PCR using methylated DNA specific binding protein , Quantitative PCR, pyrosequencing, and bisulfite sequencing, and most preferably may be a MIRA.

Diagnosis refers to confirming the presence or characteristic of a pathological condition, and the diagnosis of the present invention refers to confirming whether or not psoriasis has occurred.

The biological sample may be at least one selected from the group consisting of blood, urine, cells, and tissues. The cell may be any cell capable of separating a gene to be measured, preferably, it may be a CD4 ⁺ T cell.

In the present invention, "CD4 + T cell" is collectively referred to as naive CD4 ⁺ T cell, Th1 (T helper type I), Th2 (T helper type 2), T helper type 17 (Th17) and iTreg cells. Applicants collected the total T cells by negative selection and conducted the experiment (see Example 1-2). naive CD4 + cells are differentiated into Th1, Th2, Th17, and iTreg by surrounding cytokine concentrations. In the case of Th1 cells, they are differentiated by cytokines such as interferon-gamma and interleukin-12, and in the case of Th2 cells, they are differentiated by interleukin-4,2. In addition, Th17 cells are differentiated by cytokines such as TGF-β, IL-6, IL-21 and IL-23, and iTreg cells are differentiated by TGF-β and IL-2.

The genes TP73 (GenBank Accession No. NM_001126240), FANK1 (GenBank Accession No. NM_145235) and PPAPDC3 (GenBank Accession No. NM_032728) are genes that are hypermethylated in psoriasis patients than normal patients (see Example 2-3). Therefore, if the methylation level of the genes is higher than that of the normal control, it can be diagnosed as psoriasis.

The present inventors isolated total CD4 ⁺ T cells from patients with psoriasis and normal subjects, isolated genomic DNA from the cells, selected methylated DNA fragments, attempted mapping, Genes that were hypermethylated at the gene unit level were selected. The methylation genes found in the genome-wide level analysis are shown in [Table 2], and the methylation genes found in the gene unit level analysis are listed in [Table 3].

DNA methylation is a DNA methyl transferase (DNMT) that binds a methyl group (-CH ₃ ) to the 5 'carbon of CpG. CpG islands in which several CpG dinucleotides are clustered are located mainly at the promoter or at the beginning of the exon. When methyl is bonded to the CpG islands, mRNA transcription is interrupted and gene expression is suppressed (Park, Otorhinolaryngol-Head Neck Surg; 52: 943-8, 2009). Actually, genes TP73 (GenBank Accession No. NM_001126240), FANK1 (GenBank Accession No. NM_145235) and PPAPDC3 (GenBank Accession No. NM_032728) are selected from among the genes listed in [Table 2] and [Table 3] As a result of measuring the level of mRNA expression, mRNA expression rate was significantly lower than that of normal patients. The expression of 5-azacytidine, an inhibitor of methylation, on CD4 ⁺ T cells of psoriatic patients and mRNA expression was significantly higher than that of the 5-azacytidine-untreated group. That is, it can be confirmed that methylation is the cause of inhibiting mRNA expression (Examples 3 and 3).

Further, it was confirmed by the gene TR73 that methylation occurs in the gene promoter and inhibits its activity, and it was confirmed that methylation decreased the activity of the promoter (see Example 4 and Fig. 4).

Therefore, if the expression level of TP73 (GenBank Accession No. NM_001126240), FANK1 (GenBank Accession No. NM_145235) or PPAPDC3 (GenBank Accession No. NM_032728) gene is lower than that of normal control, it can be diagnosed as psoriasis.

In addition, the method may further include the step of measuring the expression level or the methylation level by selecting one or more genes among the genes listed below in addition to any one of the three genes.

GenBank Accession No. NM_019102), TPTE (GenBank Accession No. NM_199260), SPESP1 (GenBank Accession No. NM_145658), MIR200A (GenBank Accession No. NR_029834), NADK (GenBank Accession No. NR_026874), MOC663B (GenBank Accession No. NR_031608), ANKRD30BL (GenBank Accession No. NR_027020), UCN (GenBank Accession No. NM_003353), LOC100130872 (GenBank Accession No. NR_024569), SPON2 (GenBank Accession No. NM_001199021), MIR1229 (GenBank Accession No. NR_031598), C6orf201 (GenBank Accession No. NM_001085401), MEST (GenBank Accession No. NM_002402), SOHLH1 (GenBank Accession No. NM_001101677), SYCE1 (GenBank Accession No. (GenBank Accession No. NM_052997), KCNQ1DN (GenBank Accession No. NR_024627), AGAP2 (GenBank Accession No. NM_001122772), TDRD9 (GenBank Accession No. NM_153046), FAM181A (GenBank Accession No. NM_001207074), KLHL33 GenBank Accession No. NM_001109997), REREP3 (GenBank k Accession No. NR_033735), NOX5 (GenBank Accession No. Nos. GenBank Accession No. NR_038678), ALOX12 (GenBank Accession No. NM_000697), MIR3187 (GenBank Accession No. NR_036154), LOC100288123 (GenBank Accession No. NR_034114), EXOC3L2 (GenBank Accession No. NM_138568), MIR4745 GenBank Accession No. NR_039900), C19orf77 (GenBank Accession No. NM_001136503), C19orf34 (GenBank Accession No. NR_033400), MIR663 (GenBank Accession No. NR_030386), C20orf177 (GenBank Accession No. NM_001190826), GNAS (GenBank Accession No. NR_003259 ), TTLL10 (GenBank Accession No. NM_153254), FAM132A (GenBank Accession No. NM_001014980), C1orf146 (GenBank Accession No. NM_001012425), EIF2B3 (GenBank Accession No. NM_020365), CCDC27 (GenBank Accession No. NM_152492), CROCCL1 Accession No. NR_026752), FAM58B (GenBank Accession No. NM_001105517), TMEM61 (GenBank Accession No. NM_182532), OBSCN (GenBank Accession No. NM_052843), OBSCN (GenBank Accession No. NM_001098623), GPR25 (GenBank Accession No. NM_005298) , C1OrF 170 (GenBank Accession No. NR_027693), FGR (Ge nBank Accession No. (GenBank Accession No. NM_032129), GPR37L1 (GenBank Accession No. NM_032129), HSPA7 (GenBank Accession No. NR_024151), PER3 (GenBank Accession No. NM_016831), CLDN19 (GenBank Accession No. NM_001123395), MMEL1 GenBank Accession No. NM_004767), SLC25A44 (GenBank Accession No. NM_014655), ICMT (GenBank Accession No. NM_012405), KLF17 (GenBank Accession No. NM_173484), AFARP1 (GenBank Accession No. NR_002796), HIST3H3 ), OR2L13 (GenBank Accession No. NM_175911), PVRL4 (GenBank Accession No. NM_030916), EPS8L3 (GenBank Accession No. NM_139053), CLCNKA (GenBank Accession No. NM_004070), NCRNA00164 (GenBank Accession No. NR_027020), UCN Accession No. NM_003353), KRTCAP3 (GenBank Accession No. NM_173853), NCRNA00164 (GenBank Accession No. NR_027019), ANKMY1 (GenBank Accession No. NM_016552), TEKT4 (GenBank Accession No. NM_144705), LOC654433 (GenBank Accession No. NR_015377) , DNAJC5G (GenBank Accession No. NM_173650), C2orf54 (GenBank Accession No. NM_001 085437), ALPPL2 (GenBank Accession No. < / RTI > GenBank Accession No. NM_031313), KLHL30 (GenBank Accession No. NM_198582), POTEF (GenBank Accession No. NM_001099771), BOLL (GenBank Accession No. NM_033030), RGPD4 (GenBank Accession No. NM_182588), TUBA3D (GenBank Accession No. NM_080386), ARHGEF4 GenBank Accession No. NM_032995), RGPD3 (GenBank Accession No. NM_001144013), CRYGA (GenBank Accession No. NM_014617), PRLH (GenBank Accession No. NM_015893), LOC401010 (GenBank Accession No. NR_002826), MFSD2B (GenBank Accession No. NM_001080473 GenBank Accession No. NM_007046), SCTR (GenBank Accession No. NM_002980), C2orf39 (GenBank Accession No. NM_145038), NT5DC2 (GenBank Accession No. NM_022908), PRR23C (GenBank Accession No. NM_001134657), ITIH4 Accession No. NM_002218), DPPA2 (GenBank Accession No. NM_138815), RARRES1 (GenBank Accession No. NM_206963), GRK7 (GenBank Accession No. NM_139209), TM4SF19 (GenBank Accession No. NM_138461), OSTalpha (GenBank Accession No. NM_152672) , AMT (GenBank Accession No. NM_000481), PRSS50 (GenBank Accession No. NM_013270), HTR3E (GenBank Accession No. < / RTI > (GenBank Accession No. NM_014229), PRSS23 (GenBank Accession No. NM_014229), PRZ23A (GenBank Accession No. NM_001134659), SLC6A11 (GenBank Accession No. NM_014229) GenBank Accession No. NM_182702), LOC100130872 (GenBank Accession No. NR_024569), DCAF4L1 (GenBank Accession No. NM_001029955), C4orf44 (GenBank Accession No. NM_001042690), TRIM60 (GenBank Accession No. NM_152620), FAM92A3 ), ADAD1 (GenBank Accession No. NM_139243), RBM46 (GenBank Accession No. NM_144979), OTOP1 (GenBank Accession No. NM_177998), SLC26A1 (GenBank Accession No. NM_213613), RNF212 (GenBank Accession No. NM_001131034), LOC650293 Accession No. NM_001040071), ZNF595 (GenBank Accession No. NM_182524), FRG1 (GenBank Accession No. NM_004477), YTHDC1 (GenBank Accession No. NM_001031732), NAP1L5 (GenBank Accession No. NM_153757), COX7B2 (GenBank Accession No. NM_130902) , FTMT (GenBank Accession No. NM_177478), LRRC14B (GenBank Access ion No. GenBank Accession No. NM_031947), CMYA5 (GenBank Accession No. NM_153610), SLC6A19 (GenBank Accession No. NM_001003841), IL3 (GenBank Accession No. NM_000588), C5orf47 (GenBank Accession No. NM_001144954), DND1 GenBank Accession No. NM_194249), CDX1 (GenBank Accession No. NM_001804), SLC45A2 (GenBank Accession No. NM_016180), CDH9 (GenBank Accession No. NM_016279), FAM170A (GenBank Accession No. NM_182761), PDLIM4 ), PFN3 (GenBank Accession No. NM_001029886), ZDHHC11 (GenBank Accession No. NM_024786), LOC134466 (GenBank Accession No. NR_026867), PPP1R2P3 (GenBank Accession No. NR_002168), GMCL1L (GenBank Accession No. NR_003281), PLEKHG4B Accession No. NM_052909), IRX2 (GenBank Accession No. NM_033267), C6orf201 (GenBank Accession No. NM_001085401), HIST1H1A (GenBank Accession No. NM_005325), DUSP22 (GenBank Accession No. NM_020185), HDGFL1 (GenBank Accession No. NM_138574) , DDX43 (GenBank Accession No. NM_018665), PLAGL1 (GenBank Accession No. GenBank Accession No. NM_003547), DPBA5 (GenBank Accession No. NM_001025290), FAM50B (GenBank Accession No. NM_012135), FRMD1 (GenBank Accession No. NM_024919), PNLDC1 (GenBank Accession No. NM_173516), TDRD6 GenBank Accession No. NM_001010870), HUS1B (GenBank Accession No. NM_148959), ID4 (GenBank Accession No. NM_001546), MCART3P (GenBank Accession No. NR_026540), C6orf221 (GenBank Accession No. NM_001017361) , GenBank Accession No. NM_001080413, GenBank Accession No. NM_001080413), HOXA4 (GenBank Accession No. NM_002141), GPR146 (GenBank Accession No. NM_138445), ZNF716 (GenBank Accession No. NM_001159279), RAMP3 Accession No. NM_005856), AMZ1 (GenBank Accession No. NM_133463), SGCE (GenBank Accession No. NM_001099401), ELFN1 (GenBank Accession No. NM_001128636), CPA1 (GenBank Accession No. NM_001868), AMAC1L2 (GenBank Accession No. NM_054028) , TSPYL5 (GenBank Accession No. NM_033512), KIAA1875 (GenBank Accession No. NR_02 4207), DCAF4L2 (GenBank Accession No. GenBank Accession No. NM_017767), HTRA4 (GenBank Accession No. NM_153692), POTEA (GenBank Accession No. NM_001005365), PTP4A3 (GenBank Accession No. NM_032611), CSMD3 (GenBank Accession No. NM_198124), NRBP2 (GenBank Accession No. NM_0079564), GPT (GenBank Accession No. NM_0053064), GenBank Accession No. NM_0059564), LOC100130274 , GenBank Accession No. NM_022133), SOHLH1 (GenBank Accession No. NM_001080431), MAPK15 (GenBank Accession No. NM_139021), LRRC24 (GenBank Accession No. NM_001024678), RP1L1 (GenBank Accession No. NM_178857), SLC45A4 Accession No. NM_001012415), EGFL7 (GenBank Accession No. NM_016215), PTGDS (GenBank Accession No. NM_000954), NPR2 (GenBank Accession No. NM_003995), DBH (GenBank Accession No. NM_000787), NR5A1 (GenBank Accession No. NM_004959) , FAM166A (GenBank Accession No. NM_001001710), C9orf135 (GenBank Accession No. N M_001010940), MAMDC4 (GenBank Accession No. (GenBank Accession No. NM_052813), OR13J1 (GenBank Accession No. NM_001004487), C9orf152 (GenBank Accession No. NM_001012993), POMT1 (GenBank Accession No. NM_001136113), TMC1 (GenBank Accession No. NM_13691), CACNA1B GenBank Accession No. NM_000718), PRKACG (GenBank Accession No. NM_002732), PAEP (GenBank Accession No. NM_001018049), S1PR3 (GenBank Accession No. NM_005226), SNORD62A (GenBank Accession No. NR_002914), ANKRD30A (GenBank Accession No. NM_052997 ), C10orf116 (GenBank Accession No. NM_006829), GPR26 (GenBank Accession No. NM_153442), CTBP2 (GenBank Accession No. NM_022802), CCNY (GenBank Accession No. NM_181698), PNLIPRP2 (GenBank Accession No. NM_005396), PYROXD2 Accession No. NM_032709), GDF2 (GenBank Accession No. NM_016204), MMP21 (GenBank Accession No. NM_147191), CALML3 (GenBank Accession No. NM_005185), JAKMIP3 (GenBank Accession No. NM_001105521), ANKRD2 (GenBank Accession No. NM_020349) , C10orf108 (GenBank Accession No. NR_027152), IDI2 (GenBank Accession No. NM_033261), RBP3 (GenBank Accession No. 2). TUBB8 (GenBank Accession No. NM_174987), TUBGCP2 (GenBank Accession No. NM_006659), KCNQ1DN (GenBank Accession No. NR_024627), LOC441601 (GenBank Accession No. NR_003034), SPDYC (GenBank Accession No. NM_001008778), CD248 GenBank Accession No. NM_020404), TSSC4 (GenBank Accession No. NM_005706), H19 (GenBank Accession No. NR_002196), LDHAL6A (GenBank Accession No. NM_144972), FOXR1 (GenBank Accession No. NM_181721), PKP3 ), MS4A15 (GenBank Accession No. NM_001098835), MRGPRE (GenBank Accession No. NM_001039165), MUC6 (GenBank Accession No. NM_005961), LSP1 (GenBank Accession No. NM_002339), TNNT3 (GenBank Accession No. NM_006757), TP53AIP1 Accession No. NM_022112), CATSPER1 (GenBank Accession No. NM_053054), TAGLN (GenBank Accession No. NM_001001522), CABP2 (GenBank Accession No. NM_016366), GNG3 (GenBank Accession No. NM_012202) , FOLR3 (GenBank Accession No. NM_000804), TMEM218 (GenBank Accession No. NM_001080546), TBX10 (GenBank Accession No. < / RTI > (GenBank Accession No. NM_005995), SCGB2A1 (GenBank Accession No. NM_002407), C11orf36 (GenBank Accession No. NR_027138), DRD4 (GenBank Accession No. NM_000797), MUC2 (GenBank Accession No. NM_002457), AGAP2 (GenBank Accession No. NM_001122772), RPL13AP20 GenBank Accession No. NM_003932), FIGNL2 (GenBank Accession No. NM_001013690), ACRBP (GenBank Accession No. NM_032489), SLC6A12 (GenBank Accession No. NM_003044), KRT3 (GenBank Accession No. NM_057088), TUBGCP3 ), SOHLH2 (GenBank Accession No. NM_017826), ATP4B (GenBank Accession No. NM_000705), RNF17 (GenBank Accession No. NM_031277), TUBA3C (GenBank Accession No. NM_006001), CSNK1A1L (GenBank Accession No. NM_145203), DLEU7 Accession No. NM_198989), TDRD9 (GenBank Accession No. NM_153046), DIO3 (GenBank Accession No. NM_001362), COX8C (GenBank Accession No. NM_182971), ASPG (GenBank Accession No. NM_001080464), MGC23270 (GenBank Accession No. NR_024396) , RPL13AP3 (GenBank Accession No. NR_004844), RPS6KL1 (GenBank Accession No. NM_031464 ), ACOT4 (GenBank Accession No. 2). GenBank Accession No. NM_99447), GenBank Accession No. NM_022489), AMN (GenBank Accession No. NM_030943), ABHD12B (GenBank Accession No. NM_181533), TBPL2 (GenBank Accession No. NM_199047), PSMB11 GenBank Accession No. NM_001099780), CATSPER2 (GenBank Accession No. NM_054020), LOC390594 (GenBank Accession No. NM_001101362), C15orf2 (GenBank Accession No. NM_018958), PCSK6 (GenBank Accession No. NM_002570), C15orf60 (GenBank Accession No. NM_001042367 ), SNORD115-6 (GenBank Accession No. NR_003298), SNORD115-17 (GenBank Accession No. NR_003309), RASL12 (GenBank Accession No. NM_016563), SNORD115-32 (GenBank Accession No. NR_003347), SNORD115-31 (GenBank Accession No. NM_003346), LASS3 (GenBank Accession No. NM_178842), SNORD115-37 (GenBank Accession No. NR_003352), LDHAL6B (GenBank Accession No. NM_033195), GABRB3 (GenBank Accession No. NM_000814), SNORD115-25 , SLC28A2 (GenBank Accession No. NM_004212), ZNF469 (GenBank Accession No. NM_001127464), CC DC154 (GenBank Accession No. < / RTI > (GenBank Accession No. NM_027242), CLDN9 (GenBank Accession No. NM_001143980), TESSP1 (GenBank Accession No. NM_001135086), ELMO3 (GenBank Accession No. NM_024712), ZSCAN10 (GenBank Accession No. NM_032805), PDIA2 (GenBank Accession No. NM_006849), LOC146336 GenBank Accession No. NM_020982), CLDN6 (GenBank Accession No. NM_021195), IGFALS (GenBank Accession No. NM_001146006), IL34 (GenBank Accession No. NM_152456), NAT15 (GenBank Accession No. NM_001083601), SSTR5 (GenBank Accession No. NM_001053 ), DNASE1L2 (GenBank Accession No. NM_001374), MSLN (GenBank Accession No. NM_005823), CMTM1 (GenBank Accession No. NM_052999), FBRS (GenBank Accession No. NM_001105079), ZNF597 (GenBank Accession No. NM_152457), SLC5A11 Accession No. NM_052944), IL17C (GenBank Accession No. NM_013278), FAM18A (GenBank Accession No. NM_001079512), TPSG1 (GenBank Accession No. NM_012467), GPR97 (GenBank Accession No. NM_170776), PRM2 (GenBank Accession No. NM_002762) , JMJD8 (GenBank Accession No. NM_001005920), ADAD2 (GenBank Accession No. NM_13917 4), C16orf81 (GenBank Accession No. 4). (GenBank Accession No. NM_012347), TPSD1 (GenBank Accession No. NM_012217), ADCY7 (GenBank Accession No. NM_001114), ZG16B (GenBank Accession No. NM_145252), CHST5 (GenBank Accession No. NM_024533), PRR25 GenBank Accession No. NM_001089), CCDC79 (GenBank Accession No. NM_001136505), WDR59 (GenBank Accession No. NM_030581), GLIS2 (GenBank Accession No. NM_032575), MT1L (GenBank Accession No. NR_001447), TMPRSS8 (GenBank Accession No. NR_026864 ), TMC7 (GenBank Accession No. NM_024847), DNASE1 (GenBank Accession No. NM_005223), ALOX12 (GenBank Accession No. NM_000697), KCNAB3 (GenBank Accession No. NM_004732), DYSFIP1 (GenBank Accession No. NM_001007533), QRICH2 Accession No. NM_032134), FSCN2 (GenBank Accession No. NM_012418), CACNG1 (GenBank Accession No. NM_000727), TMEM88 (GenBank Accession No. NM_203411), UTS2R (GenBank Accession No. NM_018949), HSPB9 (GenBank Accession No. NM_033194) , NLGN2 (GenBank Accession No. NM_020795), FOXO3B (GenBank Accession No. NR_026718), FLJ36000 ( GenBank Accession No. GenBank Accession No. NM_006987), GGT6 (GenBank Accession No. NM_001122890), RAB34 (GenBank Accession No. NM_031934), SHISA6 (GenBank Accession No. NM_207386), GPR172B (GenBank Accession No. NM_001104577), SLFN13 GenBank Accession No. NM_144682), HSF5 (GenBank Accession No. NM_001080439), ENPP7 (GenBank Accession No. NM_178543), AIPL1 (GenBank Accession No. NM_014336), AMAC1 (GenBank Accession No. NM_152462), KCTD11 (GenBank Accession No. NM_001002914 GenBank Accession No. NM_015626), SERPINF1 (GenBank Accession No. NM_002615), ULK2 (GenBank Accession No. NM_014683), TBX4 (GenBank Accession No. NM_018488), CCDC144NL (GenBank Accession No. NM_001004306), KCNG2 Accession No. NM_012283), RNF138 (GenBank Accession No. NM_016271), ANKRD30B (GenBank Accession No. NM_001145029), PSMA8 (GenBank Accession No. NM_144662), CNDP1 (GenBank Accession No. NM_032649), EXOC3L2 (GenBank Accession No. NM_138568) , C19orf77 (GenBank Accession No. NM_001136503), C19orf34 (GenBank Accession No. GenBank Accession No. NM_031310), FJR1 (GenBank Accession No. NM_001136198), TMPRSS9 (GenBank Accession No. NM_182973), ZNF558 (GenBank Accession No. NM_144693), PLVAP (GenBank Accession No. NM_031310), YJEFN3 (GenBank Accession No. NM_198537), CCDC155 GenBank Accession No. NM_144688), TMEM86B (GenBank Accession No. NM_173804), SPACA4 (GenBank Accession No. NM_133498), PRR22 (GenBank Accession No. NM_001134316), ELANE (GenBank Accession No. NM_001972), ACPT (GenBank Accession No. NM_033068 ), PSPN (GenBank Accession No. NM_004158), WDR88 (GenBank Accession No. NM_173479), PLIN4 (GenBank Accession No. NM_001080400), OR10H1 (GenBank Accession No. NM_013940), CCDC105 (GenBank Accession No. NM_173482), SNORD37 Accession No. NR_002602), DUS3L (GenBank Accession No. NM_020175), CBLC (GenBank Accession No. NM_012116), LGALS4 (GenBank Accession No. NM_006149), COX7A1 (GenBank Accession No. NM_001864), KCNA7 (GenBank Accession No. NM_031886) , NTN5 (GenBank Accession No. NM_145807), SNORD35A (GenBank Accession No. NR_000018), FFAR2 (GenBank Accession No. 2). GenBank Accession No. NM_18572), LOC126536 (GenBank Accession No. NR_026828), LYPD4 (GenBank Accession No. NM_173506), DMRTC2 (GenBank Accession No. NM_001040283), ACTL9 (GenBank Accession No. NM_178525), TDRD12 GenBank Accession No. NM_001110822), CAPS (GenBank Accession No. NM_004058), PGLYRP1 (GenBank Accession No. NM_005091), CAPN12 (GenBank Accession No. NM_144691), FAM83E (GenBank Accession No. NM_017708), NLRP4 (GenBank Accession No. NM_134444 , GenBank Accession No. NM_003712), UPK1A (GenBank Accession No. NM_007000), INSL3 (GenBank Accession No. NM_005543), KCNJ14 (GenBank Accession No. NM_170720), ODF3L2 (GenBank Accession No. NM_182577), PLK5P Accession No. NR_026557), AURKC (GenBank Accession No. NM_001015878), ECH1 (GenBank Accession No. NM_001398), SRMS (GenBank Accession No. NM_080823), FRG1B (GenBank Accession No. NR_003579), SSTR4 (GenBank Accession No. NM_001052) , SLC12A5 (GenBank Accession No. NM_020708), L3MBTL (GenBank Accession No. NM_032107), TCEA2 (GenBank Accession No. 2). (GenBank Accession No. NM_020436), SLC13A3 (GenBank Accession No. NM_020436), and SLC13A3 (GenBank Accession No. NM_020436), FAM83C (GenBank Accession No. NM_178468), PHF20 (GenBank Accession No. NM_016436), COX4I2 (GenBank Accession No. NM_032609), CTCFL GenBank Accession No. NM_022829), MYL9 (GenBank Accession No. NM_006097), ADRA1D (GenBank Accession No. NM_000678), RTEL1 (GenBank Accession No. NM_032957), BIRC7 (GenBank Accession No. NM_139317) ), TFF1 (GenBank Accession No. NM_003225), KRTAP10-6 (GenBank Accession No. NM_198688), FTCD (GenBank Accession No. NM_006657), IGSF5 (GenBank Accession No. NM_001080444), POTED (GenBank Accession No. NM_174981) (GenBank Accession No. NM_182832), SNORA80 (GenBank Accession No. NR_002996), MOV10L1 (GenBank Accession No. NM_018995), HORMAD2 (GenBank Accession No. NM_152510), LOC400931 (GenBank Accession No. NR_027033), CACNA1I (GenBank Accession No. NM_021096), TMEM211 (GenBank Accession No. NM_001001663), BAIAP2L2 (GenBank Accession No. NM_025045), GSC2 (GenBank Accession No. < / RTI > GenBank Accession No. NM_012324), CHADL (GenBank Accession No. NM_012324), SUSD2 (GenBank Accession No. NM_019601), GGT1 (GenBank Accession No. NM_005265), RFPL2 (GenBank Accession No. NM_001098527), MCHR1 GenBank Accession No. NM_138481), RGL4 (GenBank Accession No. NM_153615), TCF20 (GenBank Accession No. NM_005650), OTUD6A (GenBank Accession No. NM_207320), FAM9A (GenBank Accession No. NM_174951), RAB40AL (GenBank Accession No. NM_001031834 ), CT45A1 (GenBank Accession No. NM_001017417), GJB1 (GenBank Accession No. NM_000166), YY2 (GenBank Accession No. NM_206923), and FAM9B (GenBank Accession No. NM_205849).

The genes described above are characterized by a high methylation level 2 to 4 times higher than that of a normal control (see Example 2-3). This characteristic of the gene is disclosed first in the present invention.

In addition, the present invention measures the expression level or methylation level of any one gene selected from the group consisting of TP73 (GenBank Accession No. NM_001126240), FANK1 (GenBank Accession No. NM_145235) and PPAPDC3 (GenBank Accession No. NM_032728) A composition for the diagnosis of psoriasis.

The term "agent for measuring the expression level of a gene" in the present invention means a molecule that can be used for detecting a marker by confirming the expression level of the mRNA or protein of the gene, which is a marker for increasing expression in psoriatic cells, And is preferably a primer that specifically binds to the gene. Refers to an antibody specifically recognized as a probe or an expression protein of the gene. More preferably, it may be a primer capable of amplifying mRNA of the gene. Most preferably, the primer may be any one or more primer pairs selected from the group consisting of the primer pairs of SEQ ID NOs: 1 and 2, the primer pairs of SEQ ID NOs: 3 and 4, and the primer pairs of SEQ ID NOs: 5 and 6.

As used herein, the term "primer" refers to a single-stranded DNA strand that can act as a starting point for template-directed DNA synthesis under suitable conditions (i. E., Four other nucleoside triphosphates and polymerase) Means an oligonucleotide. The suitable length of the primer is typically 15-30 nucleotides, although it varies depending on various factors such as temperature and use of the primer. Short primer molecules generally require lower temperatures to form sufficiently stable hybrid complexes with the template.

The sequence of the primer does not need to have a sequence completely complementary to a partial sequence of the template, and it is sufficient if the primer has sufficient complementarity within a range capable of hybridizing with the template and acting as a primer. Therefore, the primer pair in the present invention does not need to have a perfectly complementary sequence to the target gene sequence as a template, and it is sufficient that the primer pair has sufficient complementarity within a range capable of hybridizing to the sequence and acting as a primer. The primer of the present invention can be prepared with a sequence complementary to the mRNA (i.e., cDNA) sequence of the target gene. The design of such a primer can be easily carried out by those skilled in the art with reference to the cDNA sequence of the target gene.

The term "probe" means a nucleic acid fragment such as RNA or DNA corresponding to a few nucleotides or several hundreds of nucleotides that can specifically bind to an mRNA, and is labeled to confirm the presence or expression level of a specific mRNA .

The probe may be prepared in the form of an oligonucleotide probe, a single strand DNA probe, a double strand DNA probe, or an RNA probe. Hybridization was performed using a probe complementary to mRNA of TP73 (GenBank Accession No. NM_001126240), FANK1 (GenBank Accession No. NM_145235) or PPAPDC3 (GenBank Accession No. NM_032728) polynucleotide, and the expression amount of mRNA And the degree of radiation exposure can be measured. Selection of suitable probes and hybridization conditions can be appropriately selected according to techniques known in the art.

The primer or probe of the present invention can be chemically synthesized using a phosphoramidite solid support synthesis method or other well-known methods. Such nucleic acid sequences may also be modified through a variety of methods known in the art. Examples of such modifications include, but are not limited to, methylation, capping, substitution with one or more of the natural nucleotide analogs, and modifications between nucleotides, such as uncharged linkers (e.g., methylphosphonate, phosphotriester, phosphoramidate, carbamate Etc.) or charged conjugates (e.g., phosphorothioates, phosphorodithioates, etc.).

The term "antibody ", as the term is known in the art, refers to a specific immunoglobulin directed against an antigenic site. The antibody in the present invention refers to an antibody specifically binding to TP73, FANK1 or PPAPDC3 of the present invention. The TP73, FANK1 or PPAPDC3 gene is cloned into an expression vector to obtain a protein encoded by the gene , And the antibody can be prepared from the obtained protein according to a conventional method in the art. The forms of the antibodies include polyclonal or monoclonal antibodies, including all immunoglobulin antibodies. The antibody refers to a complete form having two full-length light chains and two full-length heavy chains. The antibody also includes a special antibody such as a humanized antibody.

In the present invention, the phrase "agent for measuring the level of methylation of a gene" includes a primer specific to the methylated allele sequence of the TP73, FANK1 or PPAPDC3 gene of a patient suspected of having psoriasis and a primer specific to the unmethylated allele sequence . In addition, the agent of the present invention may include a primer pair and an extension primer that are specific for the allelic sequence of the modified gene of the TP73, FANK1, or PPAPDC3 gene in psoriasis-susceptible patients.

The primers can be designed according to the sequence of the CpG islands to be subjected to methylation analysis, and each primer pair can be specifically designed to amplify cytosine that is methylated and not modified by bisulfite, It may be a pair of primers capable of specifically amplifying cytosine modified by bisulfite. It may also be a primer pair and extension primer specific for the modified sequence.

Also, in the present invention, the agent for measuring the methylation level of a gene may include a compound that modifies an unmethylated cytosine base, a primer pair specific to a modified sequence of the gene, and an extension primer.

The compound that transforms the unmethylated cytosine base may be bisulfite, but is not limited thereto, preferably sodium bisulfite. Methods for detecting the methylation of a promoter by modifying an unmethylated cytosine residue using such a bisulfite are well known in the art (Herman JG et al., 1996, Proc. Natl. Acad. Sci. USA , 93: 9821-9826; WO01 / 26536; US2003 / 0148326A1).

In addition, the methylation-sensitive restriction enzyme is a restriction enzyme capable of specifically detecting the methylation of CpG island, and is preferably a restriction enzyme containing CG as a recognition site of a restriction enzyme. For example, SmaI, SacII, EagI, HpaII, MspI, BssHII, BstUI, NotI, and the like. The methylation or non-methylation of the restriction enzyme recognition site at C may or may not be cleaved by restriction enzymes and may be detected by PCR or Southern blot analysis. Other methylation sensitive restriction enzymes than the above restriction enzymes are well known in the art.

The composition for diagnosing psoriasis according to the present invention may further contain a polymerase, agarose, buffer solution necessary for electrophoresis, etc., in addition to the above-mentioned preparation.

The present invention also relates to a pharmaceutical composition comprising a compound selected from the group consisting of TP73 (SEQ ID NO: 9 / GenBank Accession No. NM_001126240), FANK1 (SEQ ID NO: 10 / GenBank Accession No. NM_145235) and PPAPDC3 (SEQ ID NO: 11 / GenBank Accession No. NM_032728) Or a methylation level of the gene of the present invention.

The "agent for measuring the expression level or methylation level of the gene" is as described for the composition for diagnosing psoriasis.

Preferably, the psoriasis diagnostic kit may further comprise one or more other component compositions, solutions or devices suitable for the assay method. In a specific embodiment, the diagnostic kit may be a diagnostic kit comprising essential elements necessary for performing a reverse transcription-polymerase reaction. The RT-PCR kit contains the respective primers specific for the marker gene. The primer may preferably be any one or more primer pairs selected from the group consisting of the primer pairs of SEQ ID NOs: 1 and 2, the primer pairs of SEQ ID NOs: 3 and 4, and the primer pairs of SEQ ID NOs: 5 and 6. It may also contain a primer specific for the nucleic acid sequence of the control gene. Other reverse transcription polymerase reaction kits may be used in combination with test tubes or other appropriate containers, reaction buffers (varying in pH and magnesium concentration), deoxynucleotides (dNTPs), enzymes such as Taq polymerase and reverse transcriptase, DNAse, RNAse inhibitor DEPC DEPC-water, sterile water, and the like.

In another embodiment, it may be a diagnostic kit, preferably comprising an essential element necessary for carrying out a DNA chip. The DNA chip kit may include a substrate to which a cDNA or oligonucleotide corresponding to a gene or a fragment thereof is attached, and reagents, preparations, enzymes, and the like for producing a fluorescent-labeled probe. The substrate may also comprise a cDNA or oligonucleotide corresponding to a control gene or fragment thereof.

In the diagnosis of psoriasis using the expression level or methylation level of any one gene selected from the group consisting of TP73 (GenBank Accession No. NM_001126240), FANK1 (GenBank Accession No. NM_145235) and PPAPDC3 (GenBank Accession No. NM_032728) A method for providing necessary information, a composition for diagnosing psoriasis, and a diagnostic kit. The present invention is effective for diagnosing psoriasis.

FIG. 1 is a graph comparing genome-wide dMES values of psoriasis patients and atopic patients analyzed by 10 kb. (Y axis: dMES of psoriasis patients, X axis: dMES of atopic patients)
FIG. 2 is a graph comparing the gene unit MES values of psoriasis patients and atopic patients.
(Y axis in each graph: MES value of normal group, X axis: MES value of psoriasis patient or atopic patient)
3 (A) is a graph comparing mRNA expression levels of each gene (Normal: normal control group, Pso patient: psoriasis group)
FIG. 3B is a graph showing mRNA expression levels measured by 5-azacytidine (methylation inhibitor) treatment. (24-, 48-: 24 or 48 hours 5-azacytidine untreated psoriasis patients, 24 + 5aza, 48 + 5aza: 24 or 48 hours 5-azacytidine treated psoriasis patients)
FIG. 4A is a graph showing the functional analysis of the promoter region of the TP73 gene and the analysis of the function of a specific site through continuous defect analysis using the luciferase activity assay.
FIG. 4B is a graph showing the activity of methylation of the promoter region of the TP73 gene, using in vitro methylation and luciferase activity assay.

Hereinafter, the present invention will be described in detail.

However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

≪ Example 1 >

Total CD4 of peripheral blood ⁺  Securing T cell DNA

<1-1> Selection of study subjects

Patients aged 15 years or older who have not been treated for the past 2 years have 15 or 12 plaques of psoriasis and 12 atopic men and 11 normal control men. And volunteer participants who fully understand and agree with the explanatory text of the study with the approval of the Bioethics Review Committee.

<1-2> Total CD4 ⁺  T cell separation

Peripheral blood mononuclear cells (PBMCs) were obtained from the subjects by diluting them with 1 ml of physiological saline containing 2 mM EDTA and phosphate buffer solution, and then, using Ficoll-hypaque density gradient method, : peripheral blood mononuclear cells) were isolated.

MACS using (Indirect magnetic labeling system, Miltenyi Biotec Inc, CA) Total CD4 + T cell isolation kit in a PBMC isolated from peripheral blood biotin-conjugated antibody cocktail and using the biotin micro-bead of non-CD4 ⁺ T cells Total CD4 ⁺ T cells were obtained by negative selection (negative selection).

<1-3> Total CD4 ⁺  Isolation of genomic DNA from T cell

Genomic DNA was obtained from the CD4 ⁺ T cell using the DNase Blood & Tissue kit (Cat. 69504, QIAGEN, Germany) of QAIGEN. Experiments were conducted according to the kit's manual (Blood and body fluid spin protocol). Proteinase K-treated total CD4 ⁺ T cells were lysed with lysis buffer and tested according to the Blood or Body Fluid Spin Protocol. The samples were placed in DNA spin columns and centrifuged at 8000 rpm. The DNA adsorbed on the column was washed with washing buffer and then separated with elution buffer.

The amount of genomic DNA from normal CD4 ⁺ T cells in normal and psoriatic and atopic patients was measured to be about 1,800 to 20,000 ng and the purity (260/280) was measured to be about 1.9 to 2.1. Each DNA was pooled at a constant concentration of 1,500 ng and used for experiments.

&Lt; Example 2 >

Total CD4 ⁺  Comparison of DNA methylation between T cell and control group

<2-1> Selective separation of methylated DNA

Methylated CpG Island Recovery Assay (MIRA) was performed by BMC Med Genomics. 2011 Dec 2; 4: 82, J Thorac Oncol. 2012 Jan; 7 (1): 20-33. First, the region containing no CpG was cut using restriction enzyme MseI (5'-TTAA), which recognizes the TTAA sequence of genomic DNA, and the cut DNA fragment was ligated with the linker. The purified methylated DNA fragments were ligated with GST-MBD2b and His-MBD3L1 proteins, and the DNAs of nonspecific binding were removed. Then, TE buffer (Tris-HCl-QIAG) containing RNase A (100 ug, Qiagen) and Proteinase K (15ug, Qiagen) EDTA buffer) was used to recover the bound DNA.

<2-2> PCR of isolated DNA

 The recovered DNA fragment was subjected to linear amplification by PCR using a linker primer (5-TAGAATTCAGATCTCCCG-3 (SEQ ID NO: 7), lower strand sequence, 3-CTTAAGTCTAGAGGGCCCAGTGGCG-5 (SEQ ID NO: 8)). The amplified DNA was separated by gel electrophoresis and DNA of about 200-500 bp was isolated and separated by gel extraction. The isolated DNA was analyzed for genome-wide methylation using Illumina GA sequencing (Illumina Inc. USA). Sequence tags were generated using the Solexa Analysis Pipeline (version 0.3.0) at the University of California Santa Cruz [UCSC, (http://genome.ucsc.edu)] in the human genome of the NCBI Build 36.1 assembly based on the hg18 database mapping. The mapping sequencing results are compatible with the UCSC Genome Browser. To compare more specific methylation values, we transformed the sequencing data into browser extensible data (BED). The Tag distribution used was based on the Poisson distribution (Park et al., BMC Medical Genomics 2011, 4:82; J Thorac Oncol. 2012; 7: 203).

One DNA fragment was tagged every 200 bp, so that tagging was performed at a portion where methylation was high in a gene region. In order to identify the sites of methylation, the DNA fragments mapped per kb were compared with the total number of DNA fragments in the genome. Methylation Enrichment Score (MES) was adjusted by the total methylation count of genome size (15005528 * 200 bp) and was divided by the promoter size (8 * 200 bp) at 200 bp intervals The mean value of methylation count was calculated as log2.

The Methylation Enrichment Score (MES) is obtained as follows.

dMES is obtained by subtracting the MES value of the normal person from the MES value of the obtained patient, and shows the difference in the methylation level between the psoriasis patient group and the normal person group in the specific gene.

<2-3> Comparison of methylation results

1) Genome-wide analysis

We compared the differences in methylation using dMES values of psoriasis and atopy. The entire genome was divided by 10 kbp intervals, and the dMES values were averaged.

The above results are shown in Fig. 1, but in the case of psoriasis patients in Fig. 1, it can be seen that the methylation is remarkably higher in a certain region than the normal control group. In the total CD4 + T cells of patients with psoriasis, there was a change in the hypermethylation region of the DNA, resulting in a total of 866 such changes. However, there was no specific methylation change in atopic patients. The 866 hypermethylated regions found in the patients with psoriasis are listed in Table 1 below, and the genes included in the hypermethylated regions are listed in Table 2 below.

DNA methylation analysis of total CD4 + T cells in psoriasis patients (Genome-wide level) No. Chrom. Position start Position
end Psoriasis MES Normal MES (Psoriasis-Normal) MES One One 970001 980000 3.0451 1.2783 1.7668 2 One 2250001 2260000 2.3303 0.8092 1.5211 3 One 53330001 53340000 2.3887 0.9570 1.4317 4 One 1210001 1220000 2.2403 0.8526 1.3877 5 One 16820001 16830000 2.3377 0.9661 1.3716 6 One 2810001 2820000 2.1032 0.7358 1.3674 7 One 1460001 1470000 2.5663 1.2214 1.3449 8 One 3310001 3320000 2.4859 1.1581 1.3279 9 One 2320001 2330000 2.0729 0.7690 1.3039 10 One 1080001 1090000 2.0256 0.7356 1.2900 11 One 3400001 3410000 2.0860 0.8068 1.2793 12 One 3370001 3380000 1.9606 0.7098 1.2508 13 One 1140001 1150000 2.4178 1.1938 1.2241 14 One 3040001 3050000 2.0697 0.8601 1.2096 15 One 2410001 2420000 1.8344 0.6265 1.2079 16 One 2260001 2270000 2.0848 0.8828 1.2020 17 One 10640001 10650000 2.1539 0.9639 1.1900 18 One 2780001 2790000 1.9430 0.7603 1.1828 19 One 1150001 1160000 2.3005 1.1272 1.1732 20 One 1990001 2000000 2.1690 0.9992 1.1698 21 One 1900001 1910000 2.2495 1.0929 1.1566 22 One 1260001 1270000 2.4208 1.2653 1.1555 23 One 1160001 1170000 2.1042 0.9554 1.1488 24 One 1220001 1230000 2.0835 0.9370 1.1465 25 One 880001 890000 1.8152 0.6783 1.1368 26 One 1010001 1020000 2.0833 0.9480 1.1353 27 One 1.1E + 08 1.1E + 08 1.7392 0.6047 1.1345 28 One 16890001 16900000 1.6853 0.5512 1.1341 29 One 1.42E + 08 1.42E + 08 2.6178 1.4855 1.1322 30 One 10650001 10660000 1.9746 0.8460 1.1285 31 One 3500001 3510000 1.6645 0.5389 1.1255 32 One 2000001 2010000 2.2305 1.1112 1.1194 33 One 2510001 2520000 1.5944 0.4752 1.1193 34 One 10630001 10640000 2.0622 0.9460 1.1162 35 One 870001 880000 1.7169 0.6009 1.1159 36 One 3450001 3460000 2.0805 0.9821 1.0984 37 One 3210001 3220000 1.7698 0.6758 1.0940 38 One 1470001 1480000 1.8378 0.7513 1.0864 39 One 3690001 3700000 1.8196 0.7362 1.0834 40 One 3380001 3390000 1.5116 0.4383 1.0733 41 One 2270001 2280000 1.8708 0.7987 1.0721 42 One 1170001 1180000 1.5166 0.4476 1.0690 43 One 3020001 3030000 2.3193 1.2528 1.0666 44 One 1050001 1060000 2.4977 1.4327 1.0650 45 One 2790001 2800000 1.6213 0.5596 1.0617 46 One 1250001 1260000 2.1204 1.0737 1.0467 47 One 2760001 2770000 1.8431 0.7978 1.0454 48 One 2190001 2200000 1.8107 0.7687 1.0420 49 One 3410001 3420000 1.7252 0.6879 1.0374 50 One 3130001 3140000 1.9766 0.9402 1.0364 51 One 3180001 3190000 1.8948 0.8598 1.0349 52 One 2290001 2300000 1.7408 0.7060 1.0349 53 One 2090001 2100000 2.2677 1.2354 1.0323 54 One 6070001 6080000 1.6499 0.6198 1.0300 55 One 3590001 3600000 1.7368 0.7087 1.0282 56 One 3610001 3620000 1.6228 0.5951 1.0277 57 One 2220001 2230000 2.1274 1.1004 1.0270 58 One 15930001 15940000 1.5446 0.5191 1.0256 59 One 960001 970000 1.4918 0.4669 1.0250 60 One 3330001 3340000 1.8598 0.8361 1.0237 61 One 2100001 2110000 2.1751 1.1605 1.0146 62 One 1090001 1100000 1.7747 0.7633 1.0113 63 One 3460001 3470000 1.6580 0.6477 1.0103 64 One 3100001 3110000 1.6885 0.6798 1.0087 65 One 890001 900000 1.7196 0.7109 1.0087 66 One 3070001 3080000 1.5212 0.5132 1.0081 67 One 2010001 2020000 2.1803 1.1733 1.0070 68 One 2800001 2810000 1.6410 0.6408 1.0002 69 2 90960001 90970000 5.9094 4.1940 1.7155 70 2 1.33E + 08 1.33E + 08 5.6761 3.9749 1.7012 71 2 90970001 90980000 5.4519 3.8277 1.6243 72 2 1.33E + 08 1.33E + 08 7.3992 5.8036 1.5956 73 2 2.42E + 08 2.43E + 08 2.2373 0.8450 1.3924 74 2 2.42E + 08 2.42E + 08 1.8540 0.6353 1.2187 75 2 2.41E + 08 2.41E + 08 2.0362 0.8353 1.2009 76 2 2.42E + 08 2.42E + 08 1.6170 0.4470 1.1700 77 2 1.32E + 08 1.32E + 08 1.4277 0.2898 1.1379 78 2 2.39E + 08 2.39E + 08 1.8032 0.7159 1.0872 79 2 91630001 91640000 4.2877 3.2062 1.0815 80 2 2.39E + 08 2.39E + 08 2.1479 1.0893 1.0586 81 2 2.41E + 08 2.41E + 08 1.5528 0.4968 1.0560 82 2 2.42E + 08 2.42E + 08 1.4986 0.4456 1.0530 83 2 2.39E + 08 2.39E + 08 1.6331 0.5825 1.0505 84 2 2.42E + 08 2.42E + 08 1.5845 0.5344 1.0501 85 2 2.42E + 08 2.42E + 08 1.7776 0.7298 1.0478 86 2 1.33E + 08 1.33E + 08 3.8366 2.7935 1.0431 87 2 1.28E + 08 1.28E + 08 1.6198 0.5805 1.0393 88 2 10830001 10840000 1.9751 0.9384 1.0367 89 2 2.4E + 08 2.4E + 08 2.1133 1.0778 1.0355 90 2 2.41E + 08 2.41E + 08 1.7416 0.7102 1.0314 91 2 2.41E + 08 2.41E + 08 1.7762 0.7450 1.0311 92 2 3660001 3670000 1.7527 0.7496 1.0031 93 3 1.97E + 08 1.97E + 08 1.9321 0.5249 1.4072 94 3 1.99E + 08 1.99E + 08 1.8174 0.6453 1.1721 95 3 75795001 75805000 2.6158 1.4672 1.1486 96 3 11575001 11585000 1.9422 0.8197 1.1224 97 3 1.97E + 08 1.97E + 08 1.9657 0.8548 1.1109 98 3 1.97E + 08 1.97E + 08 1.6818 0.5987 1.0831 99 3 52525001 52535000 1.8092 0.7301 1.0791 100 3 1.28E + 08 1.28E + 08 1.4729 0.4080 1.0648 101 3 1.28E + 08 1.28E + 08 1.5988 0.5959 1.0029 102 4 49340001 49350000 5.2266 3.1451 2.0814 103 4 48840001 48850000 5.5060 3.5428 1.9632 104 4 48800001 48810000 4.8661 3.0339 1.8323 105 4 1770001 1780000 2.4637 0.8057 1.6581 106 4 49330001 49340000 5.1315 3.5831 1.5484 107 4 48810001 48820000 4.6725 3.1853 1.4872 108 4 700001 710000 2.1732 0.6886 1.4846 109 4 870001 880000 2.3004 0.9258 1.3746 110 4 1210001 1220000 2.5369 1.2118 1.3251 111 4 1360001 1370000 2.2544 0.9774 1.2770 112 4 1570001 1580000 2.0046 0.7315 1.2732 113 4 950001 960000 1.9872 0.7208 1.2665 114 4 1190001 1200000 1.9636 0.7492 1.2144 115 4 940001 950000 2.1963 0.9877 1.2086 116 4 1610001 1620000 1.8824 0.6822 1.2002 117 4 48790001 48800000 3.1227 1.9267 1.1960 118 4 1000001 1010000 2.1417 0.9589 1.1828 119 4 930001 940000 2.0363 0.8704 1.1659 120 4 1540001 1550000 1.5943 0.4285 1.1658 121 4 1950001 1960000 2.1529 0.9874 1.1655 122 4 1020001 1030000 1.7565 0.6198 1.1367 123 4 1510001 1520000 1.6395 0.5107 1.1288 124 4 610001 620000 1.5146 0.4040 1.1106 125 4 1340001 1350000 2.0545 0.9459 1.1086 126 4 3480001 3490000 2.2048 1.0981 1.1067 127 4 1220001 1230000 2.0495 0.9592 1.0903 128 4 2030001 2040000 1.7677 0.6801 1.0876 129 4 660001 670000 1.6491 0.5758 1.0734 130 4 1350001 1360000 2.3733 1.3051 1.0681 131 4 1500001 1510000 1.8356 0.7693 1.0663 132 4 890001 900000 2.0491 0.9851 1.0641 133 4 3490001 3500000 2.0078 0.9471 1.0607 134 4 1750001 1760000 1.5498 0.4921 1.0577 135 4 1200001 1210000 2.4282 1.3725 1.0557 136 4 1620001 1630000 1.9878 0.9450 1.0428 137 4 970001 980000 1.8630 0.8213 1.0417 138 4 3220001 3230000 1.7967 0.7631 1.0336 139 4 840001 850000 1.9791 0.9466 1.0325 140 4 1530001 1540000 1.6972 0.6666 1.0306 141 4 2910001 2920000 1.8331 0.8166 1.0166 142 4 710001 720000 2.1145 1.1015 1.0130 143 4 1580001 1590000 2.0387 1.0274 1.0114 144 4 8240001 8250000 1.4245 0.4178 1.0067 145 4 1.91E + 08 1.91E + 08 1.7010 0.6993 1.0017 146 5 1133001 1143000 2.5585 1.2176 1.3409 147 5 713001 723000 2.2720 0.9614 1.3105 148 5 1553001 1563000 2.1328 0.8882 1.2446 149 5 1113001 1123000 2.3735 1.1395 1.2340 150 5 1103001 1113000 2.2254 1.0580 1.1675 151 5 1083001 1093000 1.8162 0.6498 1.1664 152 5 533001 543000 2.0831 0.9240 1.1590 153 5 903001 913000 2.1751 1.0443 1.1308 154 5 1963001 1973000 1.6167 0.5405 1.0763 155 5 1323001 1333000 1.9984 0.9311 1.0674 156 5 553001 563000 1.7770 0.7262 1.0508 157 5 1563001 1573000 1.8822 0.8330 1.0492 158 5 1333001 1343000 1.8862 0.8433 1.0429 159 5 1343001 1353000 1.5849 0.5472 1.0377 160 5 893001 903000 1.3067 0.2700 1.0367 161 5 1.18E + 08 1.18E + 08 1.3242 0.2911 1.0331 162 5 1383001 1393000 1.8737 0.8466 1.0271 163 5 1253001 1263000 1.5608 0.5542 1.0066 164 5 483001 493000 1.8648 0.8636 1.0012 165 6 1.69E + 08 1.69E + 08 1.8409 0.4920 1.3489 166 6 1.7E + 08 1.7E + 08 1.9096 0.6489 1.2608 167 6 1.7E + 08 1.7E + 08 2.0205 0.7927 1.2278 168 6 1.7E + 08 1.7E + 08 1.9304 0.7577 1.1727 169 6 1.68E + 08 1.68E + 08 1.9964 0.8390 1.1574 170 6 1.7E + 08 1.7E + 08 1.9597 0.8292 1.1305 171 6 1.7E + 08 1.7E + 08 2.1457 1.0799 1.0658 172 6 1.69E + 08 1.69E + 08 1.7784 0.7518 1.0266 173 7 1544001 1554000 2.9617 0.9874 1.9743 174 7 1494001 1504000 3.0513 1.1983 1.8530 175 7 1484001 1494000 2.5520 0.8738 1.6782 176 7 1014001 1024000 2.6320 0.9658 1.6661 177 7 61424001 61434000 5.5090 3.9582 1.5507 178 7 1094001 1104000 2.4747 1.0754 1.3993 179 7 894001 904000 2.5789 1.1887 1.3902 180 7 1744001 1754000 2.4340 1.0639 1.3701 181 7 1914001 1924000 2.3158 0.9692 1.3466 182 7 1844001 1854000 2.2144 0.8909 1.3234 183 7 1024001 1034000 2.3392 1.0322 1.3070 184 7 1.5E + 08 1.5E + 08 2.1765 0.8754 1.3012 185 7 774001 784000 2.4406 1.1565 1.2842 186 7 984001 994000 1.8635 0.5834 1.2801 187 7 1114001 1124000 2.2091 0.9307 1.2784 188 7 1874001 1884000 1.9054 0.6360 1.2694 189 7 1814001 1824000 1.9854 0.7463 1.2391 190 7 554001 564000 2.0671 0.8500 1.2171 191 7 2664001 2674000 1.8956 0.6977 1.1979 192 7 61434001 61444000 3.5454 2.3477 1.1977 193 7 1324001 1334000 1.8624 0.6757 1.1867 194 7 2104001 2114000 1.8806 0.7009 1.1797 195 7 6654001 6664000 2.2807 1.1101 1.1706 196 7 994001 1004000 1.8486 0.6788 1.1698 197 7 61414001 61424000 3.7153 2.5539 1.1614 198 7 1.57E + 08 1.57E + 08 2.0581 0.9043 1.1538 199 7 1124001 1134000 1.9243 0.7711 1.1532 200 7 1.02E + 08 1.02E + 08 1.6614 0.5162 1.1451 201 7 5494001 5504000 1.4953 0.3508 1.1445 202 7 61384001 61394000 5.2471 4.1054 1.1417 203 7 2724001 2734000 1.7491 0.6211 1.1281 204 7 264001 274000 2.1836 1.0606 1.1230 205 7 304001 314000 2.1425 1.0216 1.1208 206 7 274001 284000 2.1771 1.0643 1.1128 207 7 4834001 4844000 2.0839 0.9735 1.1104 208 7 744001 754000 2.1327 1.0236 1.1090 209 7 634001 644000 1.7314 0.6281 1.1033 210 7 1.57E + 08 1.57E + 08 2.2802 1.1915 1.0888 211 7 1E + 08 1E + 08 1.8553 0.7670 1.0884 212 7 1.58E + 08 1.58E + 08 1.9331 0.8450 1.0882 213 7 5474001 5484000 1.4885 0.4079 1.0806 214 7 2084001 2094000 2.0607 0.9869 1.0738 215 7 1854001 1864000 2.3055 1.2337 1.0719 216 7 1.51E + 08 1.51E + 08 1.9084 0.8371 1.0714 217 7 2044001 2054000 2.2163 1.1458 1.0705 218 7 2074001 2084000 2.0252 0.9560 1.0692 219 7 2124001 2134000 1.8853 0.8200 1.0653 220 7 97674001 97684000 1.9222 0.8607 1.0615 221 7 1.58E + 08 1.58E + 08 1.9925 0.9335 1.0590 222 7 75444001 75454000 1.9307 0.8742 1.0565 223 7 2644001 2654000 1.7547 0.6985 1.0563 224 7 1474001 1484000 2.2573 1.2071 1.0502 225 7 1444001 1454000 2.0327 0.9839 1.0488 226 7 61374001 61384000 3.4986 2.4505 1.0481 227 7 1554001 1564000 1.9634 0.9211 1.0423 228 7 784001 794000 2.2589 1.2277 1.0312 229 7 57554001 57564000 3.1605 2.1344 1.0261 230 7 1894001 1904000 1.8620 0.8368 1.0252 231 7 1.57E + 08 1.57E + 08 2.3864 1.3616 1.0248 232 7 27144001 27154000 2.1431 1.1251 1.0180 233 7 2254001 2264000 1.7974 0.7800 1.0174 234 7 914001 924000 1.7506 0.7376 1.0129 235 7 1.02E + 08 1.02E + 08 2.0360 1.0255 1.0105 236 7 1054001 1064000 1.6003 0.5919 1.0084 237 7 1.49E + 08 1.49E + 08 1.5613 0.5574 1.0039 238 7 1004001 1014000 1.8470 0.8432 1.0038 239 8 1.45E + 08 1.45E + 08 2.9958 1.3330 1.6628 240 8 1.44E + 08 1.44E + 08 2.5048 0.8769 1.6279 241 8 1.45E + 08 1.45E + 08 2.5301 1.1752 1.3548 242 8 1.46E + 08 1.46E + 08 2.0550 0.7163 1.3386 243 8 1.45E + 08 1.45E + 08 2.0814 0.8214 1.2600 244 8 1.45E + 08 1.45E + 08 2.2143 0.9606 1.2537 245 8 1.46E + 08 1.46E + 08 1.7950 0.5812 1.2138 246 8 1.43E + 08 1.43E + 08 1.8345 0.6255 1.2090 247 8 47460001 47470000 1.7017 0.5174 1.1843 248 8 1.46E + 08 1.46E + 08 2.0037 0.8316 1.1721 249 8 1.42E + 08 1.42E + 08 2.0553 0.9416 1.1137 250 8 28980001 28990000 1.8578 0.7477 1.1102 251 8 1.43E + 08 1.43E + 08 1.9661 0.8727 1.0935 252 8 1.43E + 08 1.43E + 08 1.7819 0.6920 1.0899 253 8 1.46E + 08 1.46E + 08 1.5031 0.4322 1.0709 254 8 1.43E + 08 1.43E + 08 1.5033 0.4376 1.0656 255 8 1.46E + 08 1.46E + 08 1.9376 0.8931 1.0445 256 8 1.45E + 08 1.45E + 08 1.6722 0.6305 1.0416 257 8 1.45E + 08 1.45E + 08 1.6481 0.6160 1.0321 258 8 1.46E + 08 1.46E + 08 1.4914 0.4594 1.0320 259 8 1.45E + 08 1.45E + 08 1.5444 0.5183 1.0261 260 8 1420001 1430000 1.7395 0.7150 1.0245 261 8 1.44E + 08 1.44E + 08 1.5678 0.5445 1.0233 262 8 1.46E + 08 1.46E + 08 1.7044 0.6821 1.0223 263 8 1.45E + 08 1.45E + 08 1.4919 0.4699 1.0220 264 8 1120001 1130000 2.1611 1.1424 1.0188 265 8 1.45E + 08 1.45E + 08 1.7174 0.7105 1.0070 266 8 1.43E + 08 1.43E + 08 1.4652 0.4651 1.0001 267 9 1.39E + 08 1.39E + 08 2.4909 0.8077 1.6832 268 9 1.38E + 08 1.38E + 08 2.2961 0.7795 1.5166 269 9 1.39E + 08 1.39E + 08 2.7442 1.2341 1.5101 270 9 1.39E + 08 1.39E + 08 2.0880 0.6299 1.4581 271 9 1.39E + 08 1.39E + 08 2.4538 1.0611 1.3926 272 9 1.38E + 08 1.38E + 08 2.1869 0.8450 1.3418 273 9 1.39E + 08 1.39E + 08 2.2370 0.9249 1.3121 274 9 1.39E + 08 1.39E + 08 1.9656 0.6663 1.2993 275 9 1.38E + 08 1.38E + 08 2.0878 0.7902 1.2976 276 9 1.39E + 08 1.39E + 08 2.5252 1.2556 1.2695 277 9 1.4E + 08 1.4E + 08 2.0951 0.8312 1.2640 278 9 1.39E + 08 1.39E + 08 1.6412 0.4619 1.1793 279 9 1.39E + 08 1.39E + 08 1.6487 0.4823 1.1664 280 9 1.33E + 08 1.33E + 08 1.6991 0.5503 1.1489 281 9 1.38E + 08 1.38E + 08 1.8940 0.7467 1.1472 282 9 1.39E + 08 1.39E + 08 2.1300 0.9938 1.1362 283 9 1.39E + 08 1.39E + 08 1.6639 0.5352 1.1287 284 9 1.4E + 08 1.4E + 08 1.8541 0.7297 1.1243 285 9 1.39E + 08 1.39E + 08 1.9550 0.8442 1.1109 286 9 1.39E + 08 1.39E + 08 2.3609 1.2541 1.1067 287 9 1.38E + 08 1.38E + 08 2.0225 0.9167 1.1059 288 9 1.38E + 08 1.38E + 08 1.8768 0.7729 1.1039 289 9 1.37E + 08 1.37E + 08 1.7094 0.6145 1.0950 290 9 44810001 44820000 2.4538 1.3615 1.0923 291 9 1.3E + 08 1.3E + 08 1.6225 0.5417 1.0809 292 9 1.38E + 08 1.38E + 08 1.8081 0.7303 1.0778 293 9 1.38E + 08 1.38E + 08 1.9288 0.8519 1.0769 294 9 1.38E + 08 1.38E + 08 2.1856 1.1140 1.0716 295 9 1.39E + 08 1.39E + 08 2.1815 1.1131 1.0684 296 9 1.36E + 08 1.36E + 08 1.7293 0.6617 1.0677 297 9 1.36E + 08 1.36E + 08 1.8366 0.7690 1.0676 298 9 1.38E + 08 1.38E + 08 2.0394 0.9790 1.0604 299 9 1.38E + 08 1.38E + 08 1.8588 0.8003 1.0585 300 9 1.39E + 08 1.39E + 08 1.8894 0.8335 1.0560 301 9 1.39E + 08 1.39E + 08 1.3111 0.2571 1.0540 302 9 1.38E + 08 1.38E + 08 1.6349 0.5869 1.0480 303 9 1.4E + 08 1.4E + 08 2.1416 1.0971 1.0445 304 9 1.36E + 08 1.36E + 08 1.6864 0.6467 1.0397 305 9 1.38E + 08 1.38E + 08 1.6895 0.6506 1.0389 306 9 1.38E + 08 1.38E + 08 1.7171 0.6892 1.0278 307 9 1.39E + 08 1.39E + 08 1.7530 0.7298 1.0232 308 9 1.39E + 08 1.39E + 08 1.4821 0.4594 1.0227 309 9 1.39E + 08 1.39E + 08 1.7650 0.7446 1.0205 310 9 1.39E + 08 1.39E + 08 1.7876 0.7703 1.0173 311 9 1.39E + 08 1.39E + 08 1.3824 0.3656 1.0169 312 9 1.38E + 08 1.38E + 08 1.5502 0.5343 1.0159 313 9 1.39E + 08 1.39E + 08 1.6997 0.6854 1.0143 314 9 1.35E + 08 1.35E + 08 1.3623 0.3505 1.0118 315 9 1.37E + 08 1.37E + 08 1.7158 0.7080 1.0078 316 9 1.35E + 08 1.35E + 08 1.7256 0.7186 1.0069 317 10 41700001 41710000 7.8785 5.8846 1.9939 318 10 41710001 41720000 8.1834 6.3690 1.8144 319 10 1.35E + 08 1.35E + 08 2.5951 1.0001 1.5950 320 10 38920001 38930000 4.7178 3.1284 1.5894 321 10 39130001 39140000 4.4495 2.9093 1.5402 322 10 41680001 41690000 4.6260 3.1351 1.4909 323 10 1.35E + 08 1.35E + 08 2.4577 0.9707 1.4870 324 10 39180001 39190000 4.6539 3.2037 1.4503 325 10 38840001 38850000 4.1122 2.6866 1.4257 326 10 39140001 39150000 4.0001 2.5819 1.4182 327 10 38910001 38920000 4.4386 3.0639 1.3747 328 10 39160001 39170000 4.3457 2.9841 1.3616 329 10 39120001 39130000 4.4053 3.0562 1.3491 330 10 41690001 41700000 4.6575 3.3157 1.3419 331 10 39170001 39180000 4.3823 3.0645 1.3178 332 10 1.34E + 08 1.34E + 08 2.0711 0.7854 1.2857 333 10 39150001 39160000 4.0146 2.7347 1.2799 334 10 1.34E + 08 1.34E + 08 2.3483 1.0702 1.2781 335 10 1.35E + 08 1.35E + 08 2.0999 0.8479 1.2520 336 10 1.35E + 08 1.35E + 08 2.3855 1.1385 1.2470 337 10 3150001 3160000 2.1767 0.9409 1.2358 338 10 1.35E + 08 1.35E + 08 2.3177 1.1065 1.2111 339 10 1.34E + 08 1.34E + 08 2.2470 1.0371 1.2099 340 10 1.35E + 08 1.35E + 08 2.0476 0.8434 1.2042 341 10 1.35E + 08 1.35E + 08 1.8840 0.6855 1.1985 342 10 1.35E + 08 1.35E + 08 2.2885 1.0929 1.1956 343 10 42130001 42140000 3.3301 2.1454 1.1847 344 10 1.35E + 08 1.35E + 08 1.9145 0.7355 1.1789 345 10 1.35E + 08 1.35E + 08 1.9690 0.8047 1.1644 346 10 38820001 38830000 3.3017 2.1411 1.1607 347 10 42120001 42130000 3.9997 2.8525 1.1473 348 10 38830001 38840000 3.4298 2.3138 1.1160 349 10 1.35E + 08 1.35E + 08 1.4827 0.3824 1.1004 350 10 38810001 38820000 3.0545 1.9555 1.0990 351 10 1.26E + 08 1.26E + 08 1.5953 0.5030 1.0923 352 10 1.35E + 08 1.35E + 08 1.7074 0.6252 1.0822 353 10 1.35E + 08 1.35E + 08 2.0909 1.0126 1.0783 354 10 1.34E + 08 1.34E + 08 2.2159 1.1445 1.0714 355 10 1.35E + 08 1.35E + 08 2.2324 1.1619 1.0705 356 10 1.34E + 08 1.34E + 08 1.8664 0.8020 1.0645 357 10 42110001 42120000 3.3968 2.3515 1.0453 358 10 1.34E + 08 1.34E + 08 1.8327 0.8028 1.0298 359 10 1.34E + 08 1.34E + 08 2.2825 1.2534 1.0291 360 10 1.35E + 08 1.35E + 08 1.8783 0.8597 1.0186 361 10 1.34E + 08 1.34E + 08 1.8408 0.8337 1.0071 362 10 1.34E + 08 1.34E + 08 1.7186 0.7140 1.0046 363 10 1.34E + 08 1.34E + 08 1.7260 0.7223 1.0037 364 11 1170001 1180000 2.2394 0.8059 1.4335 365 11 1010001 1020000 2.2710 0.8906 1.3804 366 11 470001 480000 2.1483 0.8182 1.3302 367 11 1960001 1970000 1.8764 0.5562 1.3202 368 11 1070001 1080000 2.1455 0.8581 1.2873 369 11 1430001 1440000 2.1280 0.8432 1.2848 370 11 420001 430000 1.6476 0.3693 1.2783 371 11 1020001 1030000 2.3641 1.1210 1.2431 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7591000 1.7526 0.6768 1.0758 724 19 2191001 2201000 1.7901 0.7153 1.0748 725 19 1791001 1801000 1.6891 0.6150 1.0741 726 19 991001 1001000 1.8288 0.7576 1.0711 727 19 5021001 5031000 1.8589 0.7879 1.0710 728 19 4651001 4661000 1.7192 0.6486 1.0706 729 19 4501001 4511000 1.3359 0.2659 1.0700 730 19 701001 711000 1.5876 0.5182 1.0694 731 19 40961001 40971000 1.8182 0.7528 1.0655 732 19 54841001 54851000 1.7955 0.7305 1.0650 733 19 541001 551000 1.8157 0.7524 1.0632 734 19 3521001 3531000 1.8082 0.7471 1.0610 735 19 691001 701000 1.8832 0.8287 1.0545 736 19 371001 381000 1.8093 0.7570 1.0523 737 19 10291001 10301000 1.5902 0.5420 1.0482 738 19 3591001 3601000 1.7046 0.6569 1.0477 739 19 1361001 1371000 1.7430 0.6955 1.0475 740 19 471001 481000 1.4907 0.4469 1.0437 741 19 2281001 2291000 1.7589 0.7203 1.0386 742 19 19511001 19521000 1.6774 0.6451 1.0323 743 19 2291001 2301000 2.0371 1.0051 1.0321 744 19 821001 831000 1.7949 0.7659 1.0291 745 19 3371001 3381000 1.5583 0.5297 1.0286 746 19 1061001 1071000 1.9909 0.9653 1.0256 747 19 38571001 38581000 1.8571 0.8330 1.0241 748 19 5941001 5951000 2.0200 0.9963 1.0238 749 19 61301001 61311000 1.6728 0.6536 1.0192 750 19 3751001 3761000 1.8375 0.8205 1.0170 751 19 3631001 3641000 1.4645 0.4507 1.0138 752 19 2761001 2771000 1.8326 0.8189 1.0138 753 19 7521001 7531000 1.7562 0.7439 1.0123 754 19 901001 911000 1.6917 0.6798 1.0119 755 19 1891001 1901000 1.6774 0.6668 1.0106 756 19 351001 361000 1.6098 0.6007 1.0091 757 19 18731001 18741000 1.5113 0.5031 1.0082 758 19 3051001 3061000 1.6359 0.6345 1.0014 759 19 7881001 7891000 1.5741 0.5730 1.0011 760 19 1871001 1881000 1.6814 0.6808 1.0006 761 20 61518001 61528000 2.4709 0.9620 1.5089 762 20 61658001 61668000 2.5217 1.0227 1.4990 763 20 60318001 60328000 2.3953 1.0064 1.3890 764 20 61688001 61698000 2.0269 0.7075 1.3194 765 20 60938001 60948000 1.9953 0.7470 1.2483 766 20 29278001 29288000 4.0462 2.8009 1.2453 767 20 61448001 61458000 2.0404 0.8138 1.2266 768 20 61408001 61418000 1.7515 0.5257 1.2258 769 20 61378001 61388000 2.1243 0.9578 1.1664 770 20 61788001 61798000 1.9923 0.8277 1.1645 771 20 62038001 62048000 1.8103 0.6601 1.1502 772 20 60758001 60768000 1.8524 0.7237 1.1287 773 20 61778001 61788000 1.8700 0.7441 1.1259 774 20 61058001 61068000 2.2415 1.1266 1.1149 775 20 60798001 60808000 1.6297 0.5281 1.1016 776 20 60168001 60178000 1.9358 0.8369 1.0990 777 20 61498001 61508000 1.9680 0.8870 1.0810 778 20 62028001 62038000 2.0658 0.9866 1.0792 779 20 60158001 60168000 2.1767 1.1064 1.0703 780 20 60408001 60418000 1.5570 0.4905 1.0664 781 20 62148001 62158000 1.3664 0.3041 1.0623 782 20 61338001 61348000 1.5069 0.4517 1.0552 783 20 61868001 61878000 2.0692 1.0158 1.0534 784 20 28128001 28138000 1.9768 0.9293 1.0475 785 20 61128001 61138000 1.6331 0.5878 1.0453 786 20 61508001 61518000 2.0099 0.9686 1.0413 787 20 61628001 61638000 1.8333 0.7955 1.0378 788 20 60308001 60318000 1.7148 0.6878 1.0270 789 20 61638001 61648000 1.7087 0.6817 1.0269 790 20 61568001 61578000 1.4009 0.3755 1.0254 791 20 29288001 29298000 4.1330 3.1099 1.0231 792 20 60328001 60338000 1.7302 0.7158 1.0144 793 20 25788001 25798000 1.6310 0.6179 1.0131 794 20 60398001 60408000 1.9369 0.9259 1.0110 795 20 29268001 29278000 3.8953 2.8887 1.0066 796 21 46389766 46399765 2.3479 0.8611 1.4868 797 21 44039766 44049765 2.2491 0.8185 1.4306 798 21 46239766 46249765 2.2809 0.8801 1.4008 799 21 45709766 45719765 2.3163 1.0031 1.3132 800 21 9869766 9879765 4.0489 2.7374 1.3115 801 21 45229766 45239765 2.1210 0.8254 1.2956 802 21 46369766 46379765 2.1361 0.8869 1.2493 803 21 44569766 44579765 2.2462 0.9991 1.2471 804 21 9819766 9829765 4.2810 3.0591 1.2219 805 21 46229766 46239765 2.0510 0.8339 1.2171 806 21 9799766 9809765 4.1989 2.9830 1.2159 807 21 45239766 45249765 1.9365 0.7210 1.2154 808 21 43689766 43699765 2.0516 0.8523 1.1993 809 21 45659766 45669765 1.9653 0.7803 1.1850 810 21 43659766 43669765 2.0476 0.8811 1.1665 811 21 44529766 44539765 1.7118 0.5570 1.1548 812 21 44549766 44559765 1.9978 0.8494 1.1484 813 21 45729766 45739765 2.0712 0.9321 1.1391 814 21 44609766 44619765 1.6480 0.5123 1.1357 815 21 44559766 44569765 2.1173 0.9858 1.1315 816 21 43349766 43359765 2.1602 1.0519 1.1082 817 21 14369766 14379765 2.3213 1.2213 1.1000 818 21 45569766 45579765 1.6051 0.5184 1.0867 819 21 44179766 44189765 2.0131 0.9316 1.0815 820 21 44359766 44369765 1.8347 0.7552 1.0795 821 21 9859766 9869765 3.5127 2.4338 1.0789 822 21 43999766 44009765 1.8370 0.7592 1.0778 823 21 46359766 46369765 1.5415 0.4654 1.0761 824 21 43369766 43379765 1.4393 0.3866 1.0528 825 21 46319766 46329765 1.8823 0.8409 1.0414 826 22 15230001 15240000 5.0830 3.5090 1.5741 827 22 18510001 18520000 1.7807 0.4620 1.3187 828 22 49240001 49250000 2.3515 1.0696 1.2819 829 22 49060001 49070000 2.3967 1.1871 1.2096 830 22 48410001 48420000 2.0278 0.8756 1.1522 831 22 47290001 47300000 1.9638 0.8165 1.1473 832 22 19040001 19050000 1.4406 0.2995 1.1411 833 22 45920001 45930000 2.0702 0.9471 1.1231 834 22 47870001 47880000 2.0574 0.9435 1.1139 835 22 43980001 43990000 1.6588 0.5570 1.1018 836 22 45180001 45190000 1.9689 0.9129 1.0560 837 22 45930001 45940000 2.1694 1.1136 1.0558 838 22 48700001 48710000 1.7098 0.6659 1.0439 839 22 41930001 41940000 1.6814 0.6404 1.0411 840 22 49200001 49210000 1.6811 0.6410 1.0401 841 22 49500001 49510000 1.7119 0.6851 1.0268 842 22 47330001 47340000 1.6515 0.6266 1.0249 843 22 47410001 47420000 1.7625 0.7435 1.0190 844 22 45900001 45910000 1.6459 0.6287 1.0172 845 22 45090001 45100000 1.9109 0.8947 1.0162 846 22 45300001 45310000 1.5421 0.5407 1.0014 847 Y 10640001 10650000 3.9428 2.4480 1.4949 848 Y 12350001 12360000 3.7814 2.2868 1.4945 849 Y 11930001 11940000 4.9955 3.5151 1.4805 850 Y 12370001 12380000 4.3902 2.9767 1.4135 851 Y 11910001 11920000 5.0631 3.6674 1.3957 852 Y 12320001 12330000 4.2439 2.9144 1.3295 853 Y 11940001 11950000 4.6952 3.3735 1.3217 854 Y 11920001 11930000 4.9614 3.6443 1.3171 855 Y 10630001 10640000 5.1488 3.8430 1.3058 856 Y 12140001 12150000 4.1008 2.8069 1.2939 857 Y 11710001 11720000 3.3413 2.0580 1.2834 858 Y 10620001 10630000 3.3100 2.0451 1.2649 859 Y 57380001 57390000 4.4758 3.2696 1.2062 860 Y 12330001 12340000 3.5566 2.3698 1.1868 861 Y 12360001 12370000 3.7993 2.6473 1.1520 862 Y 12110001 12120000 3.9311 2.7807 1.1504 863 Y 12340001 12350000 3.5669 2.4229 1.1440 864 Y 12310001 12320000 3.7415 2.6475 1.0941 865 Y 12150001 12160000 2.6808 1.6482 1.0327 866 Y 12130001 12140000 3.3643 2.3440 1.0202

Genomic-wide analysis included hypermethylated genes No. Chr Refgene_ID Symbol Position
start Position
end (Psoriasis-Normal)
MES CpGi One One NR_029834 MIR200A 1093105 1093195 2.3703 X 2 One NM_001198995 NADK 1672530 1679941 2.1240 X 3 One NR_026874 LOC100130417 842815 844680 2.1054 O 4 One NM_001204191 TP73 3597095 3642625 2.0636 O 5 2 NR_031608 MIR663B 132731008 132731123 2.7559 O 6 2 NR_027020 ANKRD30BL 132621636 132732012 2.3225 O 7 2 NM_003353 UCN 27383768 27384634 2.0086 O 8 4 NR_024569 LOC100130872 1179570 1192750 2.1267 O 9 4 NM_001199021 SPON2 1150720 1192750 2.1267 O 10 5 NR_031598 MIR1229 179157883 179157952 2.2805 O 11 6 NM_001085401 C6F202 4024438 4075998 2.0232 O 12 7 NM_002402 MEST 129919173 129933367 2.1118 O 13 7 NM_019102 HOXA5 27147195 27149812 2.1072 O 14 9 NM_001101677 SOHLH1 137725075 137731195 2.0734 O 15 10 NM_001143763 SYCE1 135217393 135229128 2.5107 O 16 10 NM_052997 ANKRD30A 37454790 37561501 2.4561 O 17 11 NR_024627 KCNQ1DN 2847838 2849911 2.0561 O 18 12 NM_001122772 AGAP2 56405260 56418296 2.1059 O 19 14 NM_153046 TDRD9 103464569 103588757 2.1271 O 20 14 NM_001207074 FAM181A 93463440 93465707 2.0819 X 21 14 NM_001109997 KLHL33 19966809 19973641 2.0550 O 22 15 NR_033735 REREP3 20047928 20072195 2.5617 O 23 15 NR_033671 NOX5 67009917 67136555 2.1851 O 24 15 NM_172097 CATSPER2 41718925 41728331 2.0753 O 25 16 NR_038368 NCRNA00273 33868552 33870004 2.1336 O 26 17 NM_000697 ALOX12 6840107 6854779 2.8662 O 27 19 NR_036154 MIR3187 764583 764653 2.9017 O 28 19 NR_034114 LOC100288123 1773087 1775542 2.4744 O 29 19 NM_138568 EXOC3L2 50407718 50429309 2.1947 O 30 19 NR_039900 MIR4745 755931 756023 2.1094 O 31 19 NM_001136503 C19orf77 3425404 3431540 2.0152 X 32 19 NR_033400 C19orf34 1903525 1905548 2.0059 O 33 20 NR_030386 MIR663 26136821 26136914 2.8829 O 34 20 NM_001190826 C20Fr177 57942213 57957097 2.0689 O 35 20 NR_003259 GNAS 56897574 56919642 2.0369 O 36 21 NM_199260 TPTE 9928613 10012791 2.4734 O

2) Analysis of gene unit

In order to obtain more specific results, methylation changes were investigated by gene unit. We examined the methylation changes of promoter and gene body for each chromosome of psoriasis and atopy.

The results are shown in FIG. 2, which shows that the total CD4 + cell DNA promoter and the genebody portion of psoriasis patients were over-methylated. As with genome-wide analysis, atopic patients did not have any specific methylation changes.

In the total CD4 + T cell of patients with psoriasis, 430 genes were obtained when the dMES value of the hypermethylated promoter was 1 or more (2-fold increase in methylation compared with normal) (CpGI) was found in 217 genes and 213 genes in CpG island. The 430 genes found above are listed in Table 3 below.

In the promoter of total CD4 + T cell of psoriasis patients, genes with hypermethylated dMES value of 1 or more No. Chr Refgene_ID Symbol Position
start Position
end Psoriasis
MES Normal
MES (Psoriasis-Normal)
MES CpGI One One NM_001126240 TP73 3597095 3640327 1.0489 3.0904 2.0415 O 2 One NM_153254 TTLL10 1104939 1111106 1.2989 3.0192 1.7204 O 3 One NM_001014980 FAM132A 1167695 1171965 0.4997 2.2108 1.7111 O 4 One NM_001012425 C1orf146 92456160 92483955 0.7850 2.4322 1.6471 O 5 One NM_020365 EIF2B3 45088780 45224948 0.0623 1.7054 1.6431 O 6 One NM_152492 CCDC27 3658824 3678069 0.0623 1.6309 1.5685 X 7 One NR_026752 CROCCL1 16817339 16829988 1.7105 3.2463 1.5358 X 8 One NM_001105517 FAM58B 198449278 198450266 0.8494 2.3344 1.4850 X 9 One NM_182532 TMEM61 55219052 55230554 0.2276 1.7002 1.4726 O 10 One NM_052843 OBSCN 226462483 226615574 0.0000 1.3744 1.3744 X 11 One NM_001098623 OBSCN 226462483 226633198 0.0000 1.3744 1.3744 X 12 One NM_005298 GPR25 199108788 199109874 0.5832 1.9536 1.3704 O 13 One NR_027693 C1orf170 900441 907336 1.3381 2.7036 1.3655 X 14 One NM_005248 FGR 27811387 27834314 0.5725 1.8356 1.2631 O 15 One NR_024151 HSPA7 159842472 159844965 0.5399 1.7741 1.2342 X 16 One NM_016831 PER3 7767349 7827824 0.3522 1.5603 1.2081 O 17 One NM_001123395 CLDN19 42971350 42978512 0.5782 1.7758 1.1976 X 18 One NM_033467 MMEL1 2511940 2554341 0.0623 1.2463 1.1840 X 19 One NM_032129 PLEKHN1 891739 900345 0.0623 1.2226 1.1603 O 20 One NM_004767 GPR37L1 200358651 200365257 0.5608 1.7021 1.1412 X 21 One NM_014655 SLC25A44 154430353 154449210 0.3228 1.4425 1.1197 O 22 One NM_012405 ICMT 6203839 6218631 0.0623 1.1510 1.0887 O 23 One NM_173484 KLF17 44357108 44373396 0.4944 1.5694 1.0750 X 24 One NR_002796 AFARP1 113267494 113268818 0.1870 1.2521 1.0650 X 25 One NM_003493 HIST3H3 226679168 226679649 1.0628 2.1220 1.0592 O 26 One NM_175911 OR2L13 246167115 246330847 0.9792 2.0368 1.0576 O 27 One NM_030916 PVRL4 159307404 159326009 0.3851 1.4356 1.0504 X 28 One NM_139053 EPS8L3 110094224 110108087 0.0623 1.0892 1.0269 X 29 One NM_004070 CLCNKA 16221072 16233132 0.2276 1.2332 1.0056 X 30 2 NR_027020 NCRNA00164 132621638 132732012 4.3573 6.3274 1.9701 X 31 2 NM_003353 UCN 27383768 27384634 0.3747 2.2876 1.9129 O 32 2 NM_173853 KRTCAP3 27518736 27520667 0.9636 2.7813 1.8177 O 33 2 NR_027019 NCRNA00164 132621638 132635995 0.4149 2.0748 1.6599 X 34 2 NM_016552 ANKMY1 241067511 241146078 0.1873 1.8262 1.6389 O 35 2 NM_144705 TEKT4 94900958 94906295 0.5728 2.0601 1.4873 O 36 2 NR_015377 LOC654433 113710316 113741050 0.9355 2.4111 1.4756 X 37 2 NM_173650 DNAJC5G 27351792 27357800 0.5484 1.9900 1.4416 X 38 2 NM_001085437 C2OF54 241474137 241484246 0.6975 2.0769 1.3795 X 39 2 NM_031313 ALPPL2 232979795 232983669 0.1978 1.5384 1.3407 X 40 2 NM_198582 KLHL30 238714155 238726286 1.1042 2.4340 1.3299 O 41 2 NM_001099771 POTEF 130547577 130603265 0.0000 1.3063 1.3063 O 42 2 NM_033030 BOLL 198299847 198358319 1.1943 2.4943 1.3001 O 43 2 NM_182588 RGPD4 107809819 107875431 0.4370 1.6382 1.2012 X 44 2 NM_080386 TUBA3D 131950135 131956977 0.7136 1.9052 1.1916 O 45 2 NM_032995 ARHGEF4 131390693 131521306 0.9528 2.1391 1.1863 O 46 2 NM_001144013 RGPD3 106387567 106451233 0.3851 1.5136 1.1285 X 47 2 NM_014617 CRYGA 208733708 208736542 0.1978 1.3099 1.1121 X 48 2 NM_015893 PRLH 238139955 238140557 0.6600 1.7512 1.0912 X 49 2 NR_002826 LOC401010 131916205 131918937 0.8664 1.9529 1.0865 X 50 2 NM_001080473 MFSD2B 24086456 24100649 0.2497 1.3201 1.0704 O 51 2 NM_007046 EMILIN1 27154938 27162767 0.5175 1.5654 1.0479 X 52 2 NM_002980 SCTR 119913888 119998498 0.4552 1.4766 1.0215 O 53 2 NM_145038 C2orf39 26478287 26533083 0.4552 1.4601 1.0050 O 54 3 NM_022908 NT5DC2 52533424 52544133 0.3228 1.8593 1.5365 O 55 3 NM_001134657 PRR23C 140243633 140246424 0.9100 2.3742 1.4642 X 56 3 NM_002218 ITIH4 52822046 52839757 0.4475 1.8211 1.3737 X 57 3 NM_138815 DPPA2 110495325 110518054 0.4321 1.7691 1.3370 X 58 3 NM_206963 RARRES1 159897590 159932969 0.1873 1.4719 1.2845 O 59 3 NM_139209 GRK7 142979732 143018582 0.8108 2.0850 1.2741 O 60 3 NM_138461 TM4SF19 197534815 197549655 0.3522 1.6188 1.2666 X 61 3 NM_152672 OSTalpha 197427779 197444696 0.4772 1.7399 1.2627 X 62 3 NM_000481 AMT 49429215 49435115 0.1978 1.3911 1.1933 X 63 3 NM_013270 PRSS50 46728609 46734377 0.6235 1.8147 1.1912 O 64 3 NM_182589 HTR3E 185300660 185307477 0.2899 1.4608 1.1709 X 65 3 NM_173359 EIF4E3 71811131 71886614 0.8437 2.0042 1.1605 O 66 3 NM_032242 PLXNA1 128190126 128238925 0.5101 1.6706 1.1604 O 67 3 NM_001351 DAZL 16603304 16622010 1.1943 2.2971 1.1028 O 68 3 NM_001134659 PRR23A 140205494 140207800 1.3836 2.4114 1.0277 X 69 3 NM_014229 SLC6A11 10832916 10955146 0.7377 1.7502 1.0125 O 70 3 NM_182702 PRSS42 46846897 46850589 0.8956 1.8958 1.0002 O 71 4 NR_024569 LOC100130872 1179571 1192750 0.6127 2.6941 2.0814 X 72 4 NM_001029955 DCAF4L1 41678469 41683241 0.9426 2.9808 2.0383 O 73 4 NM_001042690 C4orf44 3220564 3228140 1.3820 3.3100 1.9280 O 74 4 NM_152620 TRIM60 166172600 166182346 1.2606 2.8881 1.6275 X 75 4 NR_003612 FAM92A3 184195811 184198266 0.6858 2.0855 1.3996 X 76 4 NM_139243 ADAD1 123519570 123570396 0.3848 1.7399 1.3551 O 77 4 NM_144979 RBM46 155921876 155969414 1.1963 2.5229 1.3266 O 78 4 NM_177998 OTOP1 4241430 4279522 0.4254 1.7515 1.3262 O 79 4 NM_213613 SLC26A1 971444 977224 0.3225 1.6217 1.2993 X 80 4 NM_001131034 RNF212 1055268 1097582 0.8740 2.1293 1.2553 X 81 4 NM_001040071 LOC650293 9094611 9095260 0.1355 1.2924 1.1570 X 82 4 NM_182524 ZNF595 43226 78099 3.2949 4.4398 1.1449 O 83 4 NM_004477 FRG1 191098967 191121353 2.4232 3.5499 1.1268 O 84 4 NM_001031732 YTHDC1 68858699 68898419 0.1978 1.2770 1.0792 O 85 4 NM_153757 NAP1L5 89836096 89838046 0.7485 1.8274 1.0789 X 86 4 NM_130902 COX7B2 46431603 46606009 0.8000 1.8166 1.0165 X 87 5 NM_177478 FTMT 121215548 121216422 0.9579 2.7705 1.8126 O 88 5 NM_001080478 LRRC14B 244625 248468 0.2497 1.9462 1.6965 O 89 5 NM_031947 SLC25A2 140662379 140663796 1.0279 2.6948 1.6669 O 90 5 NM_153610 CMYA5 79021414 79131805 1.3893 2.8316 1.4423 X 91 5 NM_001003841 SLC6A19 1254709 1278230 1.0713 2.4818 1.4106 O 92 5 NM_000588 IL3 131424245 131426795 0.1978 1.4862 1.2885 X 93 5 NM_001144954 C5orf47 173348767 173365748 1.1038 2.3917 1.2879 X 94 5 NM_194249 DND1 140030564 140033355 0.8956 2.1766 1.2810 O 95 5 NM_001804 CDX1 149526536 149544314 0.7918 1.9640 1.1722 O 96 5 NM_016180 SLC45A2 33980477 34020537 0.4552 1.5920 1.1369 X 97 5 NM_016279 CDH9 26916465 27074446 0.4254 1.5394 1.1140 X 98 5 NM_182761 FAM170A 118993152 118999415 0.3630 1.4638 1.1008 X 99 5 NM_003687 PDLIM4 131621249 131637044 0.3228 1.4199 1.0971 O 100 5 NM_001029886 PFN3 176759713 176760243 1.6152 2.7098 1.0947 O 101 5 NM_024786 ZDHHC11 848719 904101 0.6456 1.7361 1.0905 X 102 5 NR_026867 LOC134466 150290190 150306339 0.2276 1.3163 1.0887 X 103 5 NR_002168 PPP1R2P3 156210126 156212117 0.4582 1.5208 1.0626 X 104 5 NR_003281 GMCL1L 177544116 177547039 0.4582 1.5084 1.0501 X 105 5 NM_052909 PLEKHG4B 193372 243087 0.4146 1.4396 1.0250 X 106 5 NM_033267 IRX2 2799280 2804769 0.0000 1.0161 1.0161 O 107 6 NM_001085401 C6F202 4024438 4075998 1.1449 3.1979 2.0530 O 108 6 NM_005325 HIST1H1A 26125238 26126019 0.5101 2.3520 1.8418 X 109 6 NM_020185 DUSP22 237100 296355 0.8000 2.5608 1.7608 O 110 6 NM_138574 HDGFL1 22677656 22678729 0.7706 2.5111 1.7405 O 111 6 NM_018665 DDX43 74161005 74184003 0.1873 1.8589 1.6715 O 112 6 NM_006718 PLAGL1 144303129 144371234 1.0415 2.6051 1.5636 O 113 6 NM_003547 HIST1H4G 26354817 26355184 1.4082 2.9026 1.4944 O 114 6 NM_001025290 DPPA5 74119507 74120674 1.2535 2.6036 1.3501 O 115 6 NM_012135 FAM50B 3794630 3796550 0.9338 2.2743 1.3404 O 116 6 NM_024919 FRMD1 168199312 168222688 0.7706 1.9845 1.2139 O 117 6 NM_173516 PNLDC1 160141290 160161725 1.2221 2.3708 1.1488 O 118 6 NM_001010870 TDRD6 46763570 46780013 1.6860 2.8069 1.1209 O 119 6 NM_148959 HUS1B 600938 601964 0.5098 1.5758 1.0660 O 120 6 NM_001546 ID4 19945595 19948894 0.8922 1.9187 1.0266 O 121 6 NR_026540 MCART3P 66554492 66556096 1.4273 2.4509 1.0237 X 122 6 NM_001017361 C6F221 74129120 74130619 0.7377 1.7406 1.0029 X 123 7 NM_019102 HOXA5 27147520 27149812 1.2660 3.6642 2.3983 O 124 7 NM_002402 MEST 129919173 129933367 0.7598 2.8716 2.1118 O 125 7 NM_177455 BHLHA15 97679501 97680207 0.9463 2.4861 1.5398 O 126 7 NM_001080413 NOBOX 143725265 143731719 0.5098 2.0390 1.5292 X 127 7 NM_002141 HOXA4 27134650 27136924 0.9471 2.3330 1.3858 O 128 7 NM_138445 GPR146 1063666 1065423 1.0605 2.3475 1.2870 O 129 7 NM_001159279 ZNF716 57513824 57537207 0.1247 1.2694 1.1447 X 130 7 NM_005856 RAMP3 45163891 45190375 0.0000 1.1324 1.1324 O 131 7 NM_133463 AMZ1 2685688 2721595 0.4064 1.4862 1.0798 O 132 7 NM_001099401 SGCE 94052471 94123457 0.8743 1.9058 1.0314 O 133 7 NM_001128636 ELFN1 1715323 1754116 0.6646 1.6736 1.0090 X 134 7 NM_001868 CPA1 129807525 129815184 0.5782 1.5811 1.0030 X 135 8 NM_054028 AMAC1L2 11225904 11227105 0.1355 1.7374 1.6020 X 136 8 NM_033512 TSPYL5 98354889 98359352 0.1247 1.7251 1.6004 O 137 8 NR_024207 KIAA1875 145234616 145245206 0.5620 2.1326 1.5706 X 138 8 NM_152418 DCAF4L2 88952088 88955412 1.5438 3.1136 1.5698 O 139 8 NM_017767 SLC39A4 145608605 145612725 0.6646 2.2334 1.5688 O 140 8 NM_153692 HTRA4 38950824 38965331 0.3120 1.8658 1.5538 O 141 8 NM_001005365 POTEA 43266741 43337485 0.8743 2.3280 1.4537 X 142 8 NM_032611 PTP4A3 142501188 142510802 0.8542 2.1968 1.3427 X 143 8 NM_198124 CSMD3 113304332 114458558 0.1247 1.4261 1.3014 X 144 8 NM_178564 NRBP2 144987903 144996188 0.3117 1.6084 1.2967 O 145 8 NM_001162914 LOC100130274 144860852 144862267 1.6863 2.9560 1.2697 X 146 8 NM_001100878 C8orf73 144719505 144726071 0.2709 1.5398 1.2689 X 147 8 NM_178172 GPIHBP1 144366442 144370418 0.3959 1.6296 1.2337 X 148 8 NM_003695 LY6D 143863299 143865010 0.6734 1.8980 1.2247 X 149 8 NM_005309 GPT 145700272 145703363 0.4772 1.6761 1.1988 X 150 8 NM_139021 MAPK15 144870494 144876621 0.6926 1.8844 1.1919 O 151 8 NM_001024678 LRRC24 145718569 145723224 1.2797 2.4692 1.1895 O 152 8 NM_178857 RP1L1 10501269 10550027 0.3120 1.3860 1.0740 X 153 8 NM_001080431 SLC45A4 142290051 142307855 0.3228 1.3852 1.0624 X 154 8 NM_022133 SNX16 82874372 82917076 1.6537 2.6747 1.0210 X 155 9 NM_001012415 SOHLH1 137725075 137731195 0.7184 2.6563 1.9380 O 156 9 NM_032728 PPAPDC3 133154901 133174470 1.0451 2.8790 1.8339 X 157 9 NM_016215 EGFL7 138677202 138686951 0.6232 2.3386 1.7155 X 158 9 NM_000954 PTGDS 138991776 138996015 0.4880 2.0660 1.5780 O 159 9 NM_003995 NPR2 35782405 35799728 1.1510 2.6995 1.5485 O 160 9 NM_000787 DBH 135491305 135514287 0.4993 1.9855 1.4862 X 161 9 NM_004959 NR5A1 126283335 126309520 0.2899 1.7005 1.4106 X 162 9 NM_001001710 FAM166A 139257857 139262043 0.1870 1.5233 1.3363 X 163 9 NM_001010940 C9orf135 71625550 71710968 0.2497 1.5356 1.2859 X 164 9 NM_206920 MAMDC4 138866639 138875072 0.3228 1.5216 1.1988 X 165 9 NM_052813 CARD9 138378229 138387954 0.8956 2.0875 1.1919 X 166 9 NM_001004487 OR13J1 35859459 35860398 0.6564 1.8447 1.1883 X 167 9 NM_001012993 C9orf152 112001666 112010234 0.0623 1.1852 1.1229 X 168 9 NM_001136113 POMT1 133368109 133389013 0.0623 1.1663 1.1040 X 169 9 NM_138691 TMC1 74326536 74641087 0.3228 1.4075 1.0847 X 170 9 NM_000718 CACNA1B 139892061 140138896 1.3595 2.4430 1.0835 O 171 9 NM_002732 PRKACG 70817275 70818859 0.8321 1.8862 1.0541 O 172 9 NM_001018049 PAEP 137593424 137598443 0.2709 1.3235 1.0526 X 173 9 NM_005226 S1PR3 90796181 90809745 0.6425 1.6876 1.0451 O 174 9 NR_002914 SNORD62A 133350872 133350958 0.2601 1.2620 1.0019 X 175 10 NM_052997 ANKRD30A 37454790 37561501 0.8092 3.2653 2.4561 O 176 10 NM_145235 FANK1 127575097 127688151 4.4831 6.4292 1.9460 O 177 10 NM_006829 C10orf116 88718167 88720646 0.0000 1.7077 1.7077 O 178 10 NM_153442 GPR26 125415860 125446901 0.5396 2.1113 1.5718 O 179 10 NM_022802 CTBP2 126666407 126706443 0.3959 1.9532 1.5573 X 180 10 NM_181698 CCNY 35575958 35900853 0.4552 1.7874 1.3322 X 181 10 NM_005396 PNLIPRP2 118370454 118394644 0.4149 1.6969 1.2820 X 182 10 NM_032709 PYROXD2 100133312 100164968 0.0623 1.3372 1.2748 X 183 10 NM_016204 GDF2 48033097 48036859 0.3123 1.5779 1.2655 X 184 10 NM_147191 MMP21 127445015 127454380 0.9965 2.2442 1.2477 O 185 10 NM_005185 CALML3 5556923 5558225 0.7984 2.0264 1.2280 O 186 10 NM_001105521 JAKMIP3 133768302 133848302 0.7187 1.9020 1.1833 X 187 10 NM_020349 ANKRD2 99322245 99333631 0.0000 1.1499 1.1499 X 188 10 NR_027152 C10orf108 686016 701108 0.8627 1.9589 1.0962 X 189 10 NM_033261 IDI2 1054846 1061799 0.0623 1.1548 1.0924 X 190 10 NM_002900 RBP3 48001492 48010997 0.0623 1.1345 1.0722 X 191 10 NM_177987 TUBB8 82827 85178 0.2497 1.2798 1.0301 O 192 10 NM_006659 TUBGCP2 134943127 134972634 0.4993 1.5180 1.0186 O 193 11 NR_024627 KCNQ1DN 2847838 2849909 0.5937 2.6747 2.0810 X 194 11 NR_003034 LOC441601 50195574 50214199 1.1909 2.9537 1.7628 X 195 11 NM_001008778 SPDYC 64694282 64697264 0.4254 2.0351 1.6097 X 196 11 NM_020404 CD248 65838533 65841091 0.2709 1.8729 1.6020 O 197 11 NM_005706 TSSC4 2380098 2381682 0.4997 2.0463 1.5466 X 198 11 NR_002196 H19 1972981 1975641 0.3225 1.8383 1.5158 X 199 11 NM_144972 LDHAL6A 18433949 18457723 0.4687 1.9380 1.4693 O 200 11 NM_181721 FOXR1 118347626 118357205 0.9471 2.3121 1.3650 O 201 11 NM_007183 PKP3 384216 394908 1.3277 2.6422 1.3145 O 202 11 NM_001098835 MS4A15 60280915 60300780 0.2605 1.5246 1.2642 X 203 11 NM_001039165 MRGPRE 3205616 3210192 1.4083 2.6562 1.2479 O 204 11 NM_005961 MUC6 1002823 1026706 1.5332 2.7600 1.2269 O 205 11 NM_002339 LSP1 1830775 1870069 0.0623 1.2888 1.2265 X 206 11 NM_006757 TNNT3 1897374 1916512 0.3332 1.5536 1.2203 X 207 11 NM_022112 TP53AIP1 128310479 128318032 0.7743 1.9693 1.1950 X 208 11 NM_053054 CATSPER1 65540799 65550564 0.2497 1.4386 1.1890 X 209 11 NM_001001522 TAGLN 116575249 116580718 0.4582 1.6189 1.1607 X 210 11 NM_016366 CABP2 67042993 67047475 0.3120 1.4703 1.1583 X 211 11 NM_012202 GNG3 62231689 62233253 0.6235 1.7804 1.1570 O 212 11 NM_016564 CEND1 777109 780126 0.3851 1.5071 1.1220 O 213 11 NM_000804 FOLR3 71524418 71528582 0.5101 1.5990 1.0889 X 214 11 NM_001080546 TMEM218 124471608 124478415 0.3956 1.4608 1.0652 X 215 11 NM_005995 TBX10 67155349 67163607 1.0194 2.0481 1.0288 X 216 11 NM_002407 SCGB2A1 61732715 61737987 0.0000 1.0284 1.0284 X 217 11 NR_027138 C11orf36 3196137 3200937 1.2603 2.2842 1.0239 X 218 11 NM_000797 DRD4 627304 630703 0.4769 1.4928 1.0159 O 219 11 NM_002457 MUC2 1064874 1094417 0.4254 1.4320 1.0066 X 220 12 NM_001122772 AGAP2 56405260 56418296 1.2184 3.4407 2.2223 O 221 12 NR_003932 RPL13AP20 12919677 12920336 0.1978 1.4714 1.2736 X 222 12 NM_001013690 FIGNL2 50497942 50502475 0.5101 1.7065 1.1964 O 223 12 NM_032489 ACRBP 6617502 6626841 0.5396 1.6866 1.1470 O 224 12 NM_003044 SLC6A12 169512 192753 0.0623 1.1064 1.0441 X 225 12 NM_057088 KRT3 51469735 51476159 0.0623 1.0892 1.0269 X 226 13 NM_006322 TUBGCP3 112187328 112290482 0.0623 1.4473 1.3850 O 227 13 NM_017826 SOHLH2 35640346 35686752 1.2648 2.6477 1.3829 O 228 13 NM_000705 ATP4B 113351122 113360502 1.3530 2.6953 1.3423 X 229 13 NM_031277 RNF17 24236300 24352058 1.1336 2.4743 1.3407 X 230 13 NM_006001 TUBA3C 18645917 18653936 1.2985 2.3491 1.0506 X 231 13 NM_145203 CSNK1A1L 36575397 36577801 0.9931 2.0172 1.0241 X 232 13 NM_198989 DLEU7 50184759 50315886 0.4877 1.4930 1.0053 O 233 14 NM_153046 TDRD9 103464569 103588757 1.7679 3.8950 2.1271 O 234 14 NM_001362 DIO3 101097440 101099542 0.5617 2.4645 1.9028 O 235 14 NM_182971 COX8C 92883289 92884453 0.6127 2.2180 1.6053 O 236 14 NM_001080464 ASPG 103621800 103648678 0.3332 1.6315 1.2983 O 237 14 NR_024396 MGC23270 104358582 104361100 1.1107 2.4026 1.2919 X 238 14 NR_004844 RPL13AP3 55302715 55304188 0.5206 1.7360 1.2154 X 239 14 NM_031464 RPS6KL1 74442098 74458898 0.3851 1.5899 1.2048 O 240 14 NM_152331 ACOT4 73128162 73132223 0.3332 1.5000 1.1668 O 241 14 NM_138460 CMTM5 22915856 22918821 0.3332 1.4766 1.1434 X 242 14 NM_022489 INF2 104226987 104256992 0.0623 1.1952 1.1329 O 243 14 NM_030943 AMN 102458745 102466932 0.2883 1.4124 1.1242 O 244 14 NM_181533 ABHD12B 50408627 50441438 0.1247 1.2352 1.1105 O 245 14 NM_199047 TBPL2 54950682 54977016 0.3225 1.3983 1.0758 O 246 14 NM_001099780 PSMB11 22581215 22583109 0.6388 1.7046 1.0657 X 247 15 NM_145658 SPESP1 67009918 67026202 0.6597 2.8447 2.1851 O 248 15 NM_054020 CATSPER2 41710063 41728331 0.6022 2.3873 1.7851 O 249 15 NM_001101362 LOC390594 63156206 63157583 0.7706 2.4070 1.6364 O 250 15 NM_018958 C15For2 22471633 22479686 0.7505 2.2964 1.5459 O 251 15 NM_002570 PCSK6 99661655 99847710 0.1247 1.6620 1.5373 O 252 15 NM_001042367 C15orf60 71522551 71639406 0.6646 2.0784 1.4138 O 253 15 NR_003298 SNORD115-6 22976736 22976818 0.0000 1.3301 1.3301 X 254 15 NR_003309 SNORD115-17 22999466 22999548 0.1355 1.3326 1.1972 X 255 15 NM_016563 RASL12 63132727 63147441 0.4475 1.6156 1.1682 O 256 15 NR_003347 SNORD115-32 23025206 23025288 0.1870 1.3093 1.1223 X 257 15 NR_003346 SNORD115-31 23023348 23023430 0.2497 1.3629 1.1133 X 258 15 NM_178842 LASS3 98758122 98902448 0.8715 1.9821 1.1106 O 259 15 NR_003352 SNORD115-37 23034225 23034307 0.2497 1.3311 1.0814 X 260 15 NM_033195 LDHAL6B 57286333 57288001 0.8851 1.9588 1.0736 O 261 15 NM_000814 GABRB3 24339786 24569344 0.0000 1.0614 1.0614 O 262 15 NR_003342 SNORD115-25 23011780 23011862 0.0623 1.0860 1.0236 X 263 15 NM_004212 SLC28A2 43331719 43355424 0.4370 1.4564 1.0194 X 264 16 NM_001127464 ZNF469 87021379 87034666 0.4370 2.3540 1.9170 X 265 16 NM_001143980 CCDC154 1424390 1434491 0.9060 2.7603 1.8542 X 266 16 NM_001135086 TESSP1 2788486 2795133 0.4370 2.1730 1.7360 X 267 16 NM_024712 ELMO3 65790528 65795428 0.9247 2.6258 1.7011 O 268 16 NM_032805 ZSCAN10 3078895 3082862 0.3522 2.0285 1.6762 X 269 16 NM_006849 PDIA2 273118 277210 0.6232 2.2780 1.6549 O 270 16 NR_027242 LOC146336 1054084 1068732 1.6169 3.2535 1.6366 X 271 16 NM_020982 CLDN9 3002457 3004507 0.4582 2.0921 1.6338 X 272 16 NM_021195 CLDN6 3004713 3008189 0.4237 2.0398 1.6161 O 273 16 NM_001146006 IGFALS 1780416 1783735 0.6858 2.2781 1.5923 X 274 16 NM_152456 IL34 69237968 69252085 0.6351 2.1278 1.4927 X 275 16 NM_001083601 NAT15 3433668 3476964 1.0194 2.5054 1.4860 O 276 16 NM_001053 SSTR5 1068781 1070143 1.2241 2.6866 1.4626 O 277 16 NM_001374 DNASE1L2 2226468 2228713 0.7377 2.1550 1.4173 O 278 16 NM_005823 MSLN 751133 758866 0.8712 2.1986 1.3274 X 279 16 NM_052999 CMTM1 65157850 65170539 0.9865 2.3134 1.3268 O 280 16 NM_001105079 FBRS 30583278 30589632 0.3851 1.7005 1.3154 X 281 16 NM_152457 ZNF597 3426110 3433491 0.8839 2.1980 1.3141 O 282 16 NM_052944 SLC5A11 24765052 24830445 0.7896 2.0373 1.2477 X 283 16 NM_013278 IL17C 87232501 87234383 0.0000 1.2420 1.2420 X 284 16 NM_001079512 FAM18A 10768033 10820122 0.7893 2.0287 1.2394 O 285 16 NM_012467 TPSG1 1211652 1215255 0.5782 1.8167 1.2385 X 286 16 NM_170776 GPR97 56259657 56280789 0.6022 1.8274 1.2252 X 287 16 NM_002762 PRM2 11276993 11277838 0.3228 1.5324 1.2097 O 288 16 NM_001005920 JMJD8 671667 674440 0.7380 1.9273 1.1892 O 289 16 NM_139174 ADAD2 82782223 82788273 1.2992 2.4553 1.1561 O 290 16 NR_024347 C16orf81 87753128 87757584 1.2989 2.4536 1.1548 X 291 16 NM_012217 TPSD1 1246273 1248495 0.2899 1.4426 1.1527 X 292 16 NM_001114 ADCY7 48879323 48909544 0.3228 1.4706 1.1478 X 293 16 NM_145252 ZG16B 2820173 2822286 0.7598 1.8873 1.1275 X 294 16 NM_024533 CHST5 74119928 74126569 0.7997 1.9099 1.1102 X 295 16 NM_001013638 PRR25 795443 803862 0.4877 1.5806 1.0929 X 296 16 NM_001089 ABCA3 2265879 2330748 0.1247 1.2142 1.0895 O 297 16 NM_001136505 CCDC79 65346380 65393024 1.1616 2.2497 1.0881 X 298 16 NM_030581 WDR59 73464971 73576518 0.2883 1.3633 1.0750 O 299 16 NM_032575 GLIS2 4322225 4329599 0.3225 1.3824 1.0600 X 300 16 NR_001447 MT1L 55208873 55210231 0.1873 1.2291 1.0418 X 301 16 NR_026864 TMPRSS8 2829574 2832753 0.3228 1.3563 1.0335 X 302 16 NM_024847 TMC7 18902756 18982761 0.0623 1.0792 1.0169 O 303 16 NM_005223 DNASE1 3642940 3648097 0.4149 1.4224 1.0075 X 304 17 NM_000697 ALOX12 6840107 6854779 0.3630 3.2292 2.8662 O 305 17 NM_004732 KCNAB3 7766751 7773478 0.4877 2.4451 1.9574 O 306 17 NM_001007533 DYSFIP1 77384656 77386215 0.4370 2.2723 1.8353 X 307 17 NM_032134 QRICH2 71781724 71815356 0.8437 2.5344 1.6907 O 308 17 NM_012418 FSCN2 77110011 77114631 1.2535 2.9079 1.6544 O 309 17 NM_000727 CACNG1 62471167 62483373 0.9874 2.5675 1.5801 O 310 17 NM_203411 TMEM88 7699108 7700142 1.3851 2.9495 1.5644 O 311 17 NM_018949 UTS2R 77925489 77926659 0.4756 2.0077 1.5321 O 312 17 NM_033194 HSPB9 37528281 37528897 1.3487 2.7942 1.4455 O 313 17 NM_020795 NLGN2 7252225 7263903 0.6022 2.0199 1.4177 O 314 17 NR_026718 FOXO3B 18509960 18517219 0.1247 1.5009 1.3762 X 315 17 NR_027084 FLJ36000 21828188 21837197 1.6943 3.0482 1.3539 X 316 17 NM_006987 RPH3AL 62293 202576 0.1978 1.5398 1.3420 X 317 17 NM_001122890 GGT6 4406970 4410625 0.4149 1.7427 1.3277 X 318 17 NM_031934 RAB34 24065425 24069035 0.3522 1.6567 1.3044 O 319 17 NM_207386 SHISA6 11085464 11402921 0.0000 1.2022 1.2022 X 320 17 NM_001104577 GPR172B 4876620 4879451 0.2601 1.4572 1.1971 X 321 17 NM_144682 SLFN13 30786227 30799969 0.8732 2.0398 1.1667 O 322 17 NM_001080439 HSF5 53852527 53920758 1.0780 2.2256 1.1476 O 323 17 NM_178543 ENPP7 75319476 75330616 0.0623 1.1928 1.1305 X 324 17 NM_014336 AIPL1 6267782 6279243 0.5206 1.6284 1.1078 X 325 17 NM_152462 AMAC1 30543651 30545525 0.0623 1.1680 1.1056 X 326 17 NM_001002914 KCTD11 7195931 7198986 0.3506 1.4361 1.0855 O 327 17 NM_015626 WSB1 22645232 22664772 0.1978 1.2734 1.0756 O 328 17 NM_002615 SERPINF1 1612008 1627618 0.4254 1.4963 1.0710 X 329 17 NM_014683 ULK2 19614735 19711831 0.5504 1.6064 1.0560 O 330 17 NM_018488 TBX4 56888588 56916446 0.0623 1.0730 1.0107 O 331 17 NM_001004306 CCDC144NL 20707299 20740045 0.3332 1.3384 1.0052 O 332 18 NM_012283 KCNG2 75724655 75760804 2.0522 3.8202 1.7679 O 333 18 NM_016271 RNF138 27925834 27965522 0.0000 1.2395 1.2395 O 334 18 NM_001145029 ANKRD30B 14738238 14842737 0.1873 1.4173 1.2300 X 335 18 NM_144662 PSMA8 21967813 22027317 0.4756 1.6704 1.1948 O 336 18 NM_032649 CNDP1 70352671 70403241 0.5314 1.6140 1.0826 X 337 19 NM_138568 EXOC3L2 50407718 50429309 1.0021 3.2869 2.2848 O 338 19 NM_001136503 C19orf77 3425404 3431540 0.4880 2.5763 2.0883 X 339 19 NM_152771 C19orf34 1903525 1905548 1.0415 3.0803 2.0388 O 340 19 NM_001136198 FZR1 3473953 3487755 0.6243 2.3563 1.7319 X 341 19 NM_182973 TMPRSS9 2340783 2377086 0.7377 2.3612 1.6235 X 342 19 NM_144693 ZNF558 8781381 8794565 0.6858 2.3071 1.6213 X 343 19 NM_031310 PLVAP 17323263 17349137 0.3522 1.9503 1.5981 O 344 19 NM_198537 YJEFN3 19500719 19509393 0.6661 2.1479 1.4818 O 345 19 NM_144688 CCDC155 54583317 54613058 0.3120 1.7872 1.4752 O 346 19 NM_173804 TMEM86B 60429923 60432444 0.4687 1.9383 1.4696 X 347 19 NM_133498 SPACA4 53801811 53802783 0.5396 2.0007 1.4611 X 348 19 NM_001134316 PRR22 5733970 5735776 0.7706 2.1871 1.4166 X 349 19 NM_001972 ELANE 803290 807246 0.8491 2.2623 1.4132 X 350 19 NM_033068 ACPT 55985483 55990293 0.7032 2.0964 1.3932 X 351 19 NM_004158 PSPN 6326304 6326860 1.0279 2.4155 1.3875 X 352 19 NM_173479 WDR88 38314837 38358543 0.8732 2.2249 1.3517 O 353 19 NM_001080400 PLIN4 4453191 4468716 1.1585 2.4963 1.3378 X 354 19 NM_013940 OR10H1 15778816 15779936 0.0000 1.3087 1.3087 O 355 19 NM_173482 CCDC105 14982538 14995083 0.1247 1.4273 1.3026 O 356 19 NR_002602 SNORD37 3933504 3933570 0.8740 2.1220 1.2480 X 357 19 NM_020175 DUS3L 5736154 5742249 0.2497 1.4905 1.2409 O 358 19 NM_012116 CBLC 49972965 49995742 0.6127 1.8449 1.2322 O 359 19 NM_006149 LGALS4 43984150 43995580 0.0623 1.2932 1.2309 X 360 19 NM_001864 COX7A1 41333663 41335611 0.5906 1.8184 1.2278 O 361 19 NM_031886 KCNA7 54262486 54268010 1.0367 2.2503 1.2135 O 362 19 NM_145807 NTN5 53856475 53868076 1.0888 2.2620 1.1732 X 363 19 NR_000018 SNORD35A 54686243 54686329 0.2709 1.4320 1.1611 X 364 19 NM_005306 FFAR2 40632456 40634507 0.8329 1.9759 1.1430 X 365 19 NM_182572 ZSCAN1 63237245 63257811 0.3522 1.4950 1.1428 O 366 19 NR_026828 LOC126536 15987443 15999272 0.0000 1.1345 1.1345 X 367 19 NM_173506 LYPD4 47032989 47040348 1.8610 2.9853 1.1243 O 368 19 NM_001040283 DMRTC2 47040925 47048237 1.8610 2.9853 1.1243 O 369 19 NM_178525 ACTL9 8668750 8670172 0.1355 1.2585 1.1231 O 370 19 NM_001110822 TDRD12 37902518 37973554 1.0472 2.1666 1.1194 O 371 19 NM_004058 CAPS 5865192 5867222 0.3630 1.4743 1.1112 X 372 19 NM_005091 PGLYRP1 51214280 51218163 0.2497 1.3580 1.1084 O 373 19 NM_144691 CAPN12 43912671 43926954 0.4880 1.5961 1.1080 X 374 19 NM_017708 FAM83E 53795668 53808506 0.8494 1.9478 1.0984 O 375 19 NM_134444 NLRP4 61039755 61085032 0.6492 1.7273 1.0781 O 376 19 NM_003712 PPAP2C 232043 242435 0.4993 1.5744 1.0751 O 377 19 NM_007000 UPK1A 40849554 40861207 0.3506 1.4148 1.0642 X 378 19 NM_005543 INSL3 17788321 17793320 0.2276 1.2893 1.0617 O 379 19 NM_170720 KCNJ14 53656317 53661179 0.5612 1.6043 1.0432 O 380 19 NM_182577 ODF3L2 414346 425983 1.2079 2.2510 1.0431 X 381 19 NR_026557 PLK5P 1475077 1486455 0.8000 1.8336 1.0335 X 382 19 NM_001015878 AURKC 62434239 62438728 1.2071 2.2290 1.0219 O 383 19 NM_001398 ECH1 43997901 44014337 0.5765 1.5803 1.0037 O 384 20 NM_080823 SRMS 61642606 61649301 0.9057 2.5456 1.6399 O 385 20 NR_003579 FRG1B 28225539 28247668 2.6708 4.2425 1.5718 X 386 20 NM_001052 SSTR4 22964056 22965314 1.2844 2.7905 1.5061 O 387 20 NM_020708 SLC12A5 44091227 44122196 0.1247 1.5554 1.4307 O 388 20 NM_032107 L3MBTL 41576466 41603949 0.2601 1.6820 1.4219 O 389 20 NM_198723 TCEA2 62158882 62174144 0.1873 1.5775 1.3902 O 390 20 NM_178468 FAM83C 33336700 33343639 0.8088 2.1037 1.2948 O 391 20 NM_016436 PHF20 33823336 34001702 0.1978 1.3933 1.1955 O 392 20 NM_032609 COX4I2 29689351 29696461 0.6842 1.8771 1.1929 O 393 20 NM_080618 CTCFL 55505629 55533560 0.3630 1.5210 1.1579 O 394 20 NM_020436 SALL4 49833989 49852455 0.4475 1.5920 1.1446 O 395 20 NM_022829 SLC13A3 44619869 44713505 0.2605 1.4009 1.1404 O 396 20 NM_006097 MYL9 34603310 34611640 0.7655 1.8886 1.1231 O 397 20 NM_000678 ADRA1D 4149277 4177659 0.1870 1.2507 1.0637 O 398 20 NM_032957 RTEL1 61760090 61798045 0.1355 1.1852 1.0498 O 399 20 NM_139317 BIRC7 61337720 61342299 0.1247 1.1648 1.0401 X 400 21 NM_199261 TPTE 9928613 10012791 1.3767 3.6242 2.2475 O 401 21 NM_000383 AIRE 44530190 44542530 1.0797 2.6717 1.5919 O 402 21 NM_003225 TFF1 42655459 42659713 0.3851 1.9371 1.5520 X 403 21 NM_198688 KRTAP10-6 44835576 44836814 0.3336 1.7306 1.3970 X 404 21 NM_006657 FTCD 46380603 46399909 0.8956 2.2704 1.3748 X 405 21 NM_001080444 IGSF5 40039203 40095893 0.0623 1.3705 1.3082 X 406 21 NM_174981 POTED 13904368 13935777 0.0623 1.3670 1.3047 X 407 21 NM_182832 PLAC4 41469027 41479036 0.1978 1.4930 1.2952 X 408 21 NR_002996 SNORA80 32671366 32671502 0.0000 1.0424 1.0424 X 409 22 NM_018995 MOV10L1 48870561 48942242 0.9792 2.6865 1.7074 O 410 22 NM_152510 HORMAD2 28806452 28903062 0.5101 2.1479 1.6378 O 411 22 NR_027033 LOC400931 44860540 44888470 1.2429 2.6845 1.4416 X 412 22 NM_021096 CACNA1I 38296703 38415687 0.3228 1.5727 1.2499 X 413 22 NM_001001663 TMEM211 23661207 23665314 0.1978 1.3368 1.1390 X 414 22 NM_025045 BAIAP2L2 36810841 36836622 1.1007 2.2371 1.1363 X 415 22 NM_005315 GSC2 17516503 17517796 0.1873 1.2974 1.1100 O 416 22 NM_019601 SUSD2 22907443 22915074 1.1526 2.2617 1.1090 X 417 22 NM_005265 GGT1 23329179 23354972 0.1247 1.2283 1.1037 X 418 22 NM_001098527 RFPL2 30916421 30929464 0.3851 1.4586 1.0734 X 419 22 NM_005297 MCHR1 39405127 39408764 0.0623 1.1294 1.0671 X 420 22 NM_012324 MAPK8IP2 49385996 49396845 0.0000 1.0611 1.0611 O 421 22 NM_138481 CHADL 39955459 39966881 0.1978 1.2555 1.0577 X 422 22 NM_153615 RGL4 22363047 22371363 0.3506 1.3865 1.0359 X 423 22 NM_005650 TCF20 40885962 40941389 0.3120 1.3139 1.0019 X 424 X NM_207320 OTUD6A 69199065 69200754 0.3747 2.2174 1.8427 O 425 X NM_174951 FAM9A 8718836 8729424 0.1355 1.3414 1.2060 O 426 X NM_001031834 RAB40AL 102078855 102079884 0.0623 1.2455 1.1832 O 427 X NM_001017417 CT45A1 134674850 134684654 0.2276 1.3706 1.1431 X 428 X NM_000166 GJB1 70359780 70361790 0.0000 1.1246 1.1246 X 429 X NM_206923 YY2 21784523 21785642 0.5396 1.6406 1.1010 O 430 X NM_205849 FAM9B 8953038 8961116 0.9797 2.0192 1.0395 X

&Lt; Example 3 >

mRNA Expression Comparison

The methylated gene is expected to have a low level of mRNA expression, and thus, TP73 (no.1 in [Table 3]), FANK1 (no. 176 in [Table 3]) among the genes listed in [Table 2] ) And PPAPDC3 (no. 156 in [Table 3]), and compared mRNA expression in the normal group and in the dry eye group. In addition, we have re-confirmed DNA methylation inhibitor-treated experiments.

To construct an experimental group treated with DNA methylation inhibitor, the total CD4 + T of the psoriasis patients isolated in Example < 1-2 > cells are cultured in RPMI (10% FBS) containing IL-2 (100 IU / ml) at a concentration of 1x10 ⁶ / ml. At this time, 5-azacytidine, a DNA methylation inhibitor, was treated with 10 μM and incubated for 24 hours or 48 hours. Cells were collected and RNA was extracted.

QuantiTect Rev. Transcription Kit (QIAGEN) was used to generate cDNA from the isolated RNA and then real-time PCR was performed. KAPA SYBRFAST qPCR Kits were performed on a Rotergene 6000 (Corbett, Australia). PCR was performed by Delta-Delta CT method at 95 ° C for 10 minutes, at 95 ° C for 20 seconds, at 55 ° C for 20 seconds, and at 72 ° C for 20 seconds for 40 cycles. Glyceraldehyde-3-phosphate dehydrogenase was used as a loading control.

Experimental results of group 1 (5-azacytidine untreated) and group 2 (5-azacytidine treated) were quantified using the Delta-Delta CT method of the Rotergene 6000 (Corbett, Australia) program. The T-test method was used to check the significance of each result.

The primer information used for amplification is shown in Table 4 below.

Gene name SEQ ID NO: product size TP73
Omni direction 5'-CAGATCCATGCCTCGTCC -3 '(SEQ ID NO: 1) 148 bp
Reverse 5'-CTGCTCATCTGGTCCATGG -3 '(SEQ ID NO: 2) FANK1
Omni direction 5'-AGTGGTTCAGGTTCTCGATTG -3 '(SEQ ID NO: 3) 135 bp
Reverse 5'-TGACCTTCAGGCGAAATCTG -3 '(SEQ ID NO: 4) PPAPDC3
Omni direction 5'-AGGTGCTCATGAATCTGCTC -3 '(SEQ ID NO: 5) 141 bp
Reverse 5'-GGAAGGCGTAGATGTCCATG -3 '(SEQ ID NO: 6)

The mRNA expression levels of the three genes in the normal group and the psoriasis group are shown in [A] of FIG. 3, and the total mRNA expression level of 5-azacytidine treated group and the untreated group in the total CD4 + 3]. 3 in Fig. 3, mRNA expression of the three genes was significantly reduced in the psoriasis group compared to the normal group, and in the case of 5-azacytidine treatment group in Fig. 3B, mRNA expression was increased. Thus, psoriasis diagnosis can be diagnosed by the mRNA expression level of the genes listed in [Table 2] or [Table 3].

<Example 4>

Relationship between Activation and Methylation of Promoters

&Lt; 4-1 > TP73  Activation of gene by promoter region

The promoter region of the methylated gene is cloned and its activation is measured. In the CD4 ⁺ T cell genomic DNA, cloning is carried out using the PCR method to locate about 1 kb upstream of the TP73 gene in front of the luciferase gene. That is, the function of the promoter is determined by measuring the activation of luciferase according to the action of the promoter.

Transformed T cell line Jurkat T cells were cultured in RPMI (10% FBS) at a concentration of ⁴ × 10 ⁵ / ml and treated with a mixture of 1 microgram of the vector in which the promoter was cloned and lipofectamine 2000 transfection reagent 3 microlitter. . Forty-eight hours later, the cells are collected and assayed using a lysis buffer and reagents provided by the promega dual luciferase assay system. The active measuring instrument uses a luminometer. (Figure 4A)

The relative activity is measured and expressed based on the activity of the control vector. In order to measure the activity of each region of the promoter, the promoter region that has been further sequenced is cloned and its activity is measured. This method can measure the active contribution of each site in such a way that the degree of activity of each part of the promoter can be known. (Figure 4A)

<4-2> Reduction of promoter activity due to methylation

The in vitro methylation of a promoter cloning vector identified by luciferase activation assay, followed by measurement of the activity, measures the effect of methylation.

Vectors were methylated with S-adenosyl methionine (SAM) as a methyl group-supplying substance using a CpG methylase, M.SssI enzyme, as a control vector and a vector in which a TP73 captor motor (-438 to +53) region was cloned. After the reaction, the degree of methylation is checked using a restriction enzyme sensitive to methylation (eg, NotI), and the resultant is subjected to purification through a purification process with a vector not subjected to methylation.

The methylated vectors were transfected with Jurkat T cells together with the control group in the same manner as described above, and then the activation of the promoter region with and without methylation was checked by luciferase assay to verify the effect (FIG. 4B)

A method for providing information necessary for the diagnosis of psoriasis using any one gene selected from the group consisting of TP73 (GenBank Accession No. NM_001126240), FANK1 (GenBank Accession No. NM_145235) and PPAPDC3 (GenBank Accession No. NM_032728) A composition for diagnosing psoriasis, and a diagnostic kit. The methods, compositions and kits of the present invention can be used to diagnose psoriasis and are highly industrially applicable.

<110> CATHOLIC UNIVERSITY INDUSTRY ACADEMIC COOPERATION FOUNDATION <120> Genetic Marker for Diagnosis of Psoriasis and Method for          diagnosis of Psoriasis using the same <130> NP12-0080 <160> 11 <170> Kopatentin 2.0 <210> 1 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Foward Primer for TP73 <400> 1 cagatccatg cctcgtcc 18 <210> 2 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Reverse Primer for TP73 <400> 2 ctgctcatct ggtccatgg 19 <210> 3 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Foward Primer for FANK1 <400> 3 agtggttcag gttctcgatt g 21 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Reverse Primer for FANK1 <400> 4 tgaccttcag gcgaaatctg 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Foward Primer for PPAPDC3 <400> 5 aggtgctcat gaatctgctc 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Reverse Primer for PPAPDC3 <400> 6 ggaaggcgta gatgtccatg 20 <210> 7 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Linker primer for upper strand sequence <400> 7 tagaattcag atctcccg 18 <210> 8 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Linker primer for lower strand sequence <400> 8 gcggtgaccc gggagatctg aattc 25 <210> 9 <211> 5131 <212> DNA <213> TP73 gene sequence of Homo sapiens <400> 9 ggattcagcc agttgacaga actaagggag atgggaaaag cgaaaatgcc aacaaacggc 60 ccgcatgttc cccagcatcc tcggctcctg cctcactagc tgcggagcct ctcccgctcg 120 gtccacgctg ccgggcggcc acgaccgtga cccttcccct cgggccgccc agatccatgc 180 ctcgtcccac gggacaccag ttccctggcg tgtgcagacc ccccggcgcc taccatgctg 240 tacgtcggtg accccgcacg gcacctcgcc acggcccagt tcaatctgct gagcagcacc 300 atggaccaga tgagcagccg cgcggcctcg gccagcccct acaccccaga gcacgccgcc 360 agcgtgccca cccactcgcc ctacgcacaa cccagctcca ccttcgacac catgtcgccg 420 gcgcctgtca tcccctccaa caccgactac cccggacccc accactttga ggtcactttc 480 cagcagtcca gcacggccaa gtcagccacc tggacgtact ccccgctctt gaagaaactc 540 tactgccaga tcgccaagac atgccccatc cagatcaagg tgtccacccc gccaccccca 600 ggcaccgcca tccgggccat gcctgtttac aagaaagcgg agcacgtgac cgacgtcgtg 660 aaacgctgcc ccaaccacga gctcgggagg gacttcaacg aaggacagtc tgctccagcc 720 agccacctca tccgcgtgga aggcaataat ctctcgcagt atgtggatga ccctgtcacc 780 ggcaggcaga gcgtcgtggt gccctatgag ccaccacagg tggggacgga attcaccacc 840 atcctgtaca acttcatgtg taacagcagc tgtgtagggg gcatgaaccg gcggcccatc 900 ctcatcatca tcaccctgga gatgcgggat gggcaggtgc tgggccgccg gtcctttgag 960 ggccgcatct gcgcctgtcc tggccgcgac cgaaaagctg atgaggacca ctaccgggag 1020 cagcaggccc tgaacgagag ctccgccaag aacggggccg ccagcaagcg tgccttcaag 1080 cagagccccc ctgccgtccc cgcccttggt gccggtgtga agaagcggcg gcatggagac 1140 gaggacacgt actaccttca ggtgcgaggc cgggagaact ttgagatcct gatgaagctg 1200 aaagagagcc tggagctgat ggagttggtg ccgcagccac tggtggactc ctatcggcag 1260 cagcagcagc tcctacagag gccgagtcac ctacagcccc cgtcctacgg gccggtcctc 1320 tcgcccatga acaaggtgca cgggggcatg aacaagctgc cctccgtcaa ccagctggtg 1380 ggccagcctc ccccgcacag ttcggcagct acacccaacc tggggcccgt gggccccggg 1440 atgctcaaca accatggcca cgcagtgcca gccaacggcg agatgagcag cagccacagc 1500 gcccagtcca tggtctcggg gtcccactgc actccgccac ccccctacca cgccgacccc 1560 agcctcgtca gttttttaac aggattgggg tgtccaaact gcatcgagta tttcacctcc 1620 caagggttac agagcattta ccacctgcag aacctgacca ttgaggacct gggggccctg 1680 aagatccccg agcagtaccg catgaccatc tggcggggcc tgcaggacct gaagcagggc 1740 cacgactaca gcaccgcgca gcagctgctc cgctctagca acgcggccac catctccatc 1800 ggcggctcag gggaactgca gcgccagcgg gtcatggagg ccgtgcactt ccgcgtgcgc 1860 cacaccatca ccatccccaa ccgcggcggc ccaggcggcg gccctgacga gtgggcggac 1920 ttcggcttcg acctgcccga ctgcaaggcc cgcaagcagc ccatcaagga ggagttcacg 1980 gaggccgaga tccactgagg gcctcgcctg gctgcagcct gcgccaccgc ccagagaccc 2040 aagctgcctc ccctctcctt cctgtgtgtc caaaactgcc tcaggaggca ggaccttcgg 2100 gctgtgcccg gggaaaggca aggtccggcc catccccagg cacctcacag gccccaggaa 2160 aggcccagcc accgaagccg cctgtggaca gcctgagtca cctgcagaac cttctggagc 2220 tgccctagtg ctgggcttgt ggggcggggg ctggcccact ctcagccctg ccactgcccc 2280 ggcgtgctcc atggcaggcg tgggtgggga ccgcagcgtc ggctccgact tccaggcttc 2340 atcctagaga ctgtcatctc ccaaccaggc gaggtccttc caaaggaaag gatcctcttt 2400 gctgatggac tgccaaaaag tattttgcga catcttttgg ttctggatag tagtgagcag 2460 ccaagtgact gtgtctgaaa caccagtgta ttttcaggga atgtccctaa ctgcgtcttg 2520 cccgcgccgg gggctgggga ctctctctgc tggacttggg actggcctct gcccccagca 2580 cgctgtattc tgcaggaccg cctccttcct gcccctaaca acaaccacag tgttgctgaa 2640 attggagaaa actggggagg gcgcaacccc ccccaggcgc ggggaagcat gtggtaccgc 2700 ctcagccagt gcccctcagc ctggccacag tcgcctctcc tcggggaccc ctcagcagaa 2760 agggacagcc tgtccttaga ggactggaaa ttgtcaatat ttgataaaat gatacccttt 2820 tctacatggt gggtcagctt tttttttttt ttttttaact ttctttctca gcattctctt 2880 tggagttcaa cctagcgccc atgagccagg ctgaggaagc tgagtgagaa gccaggtggg 2940 cgggacttgt tcccaggaag gccgggtggg gaggaagcct agagggaacc ccaggaaggg 3000 caaatccagg caaatctgca ggaatgctct gccatgggag cagctcctcc cttgccacgg 3060 ccaccttctc tagcactgca aggtccacag ggcattgctt tcctttctag gcggtggcag 3120 tcagggaaca gactgaggta ggtgtagggg ggtctaggcc ttcgtggagc accccaggga 3180 gttagtaggc cccggggaga cagagtctgc acaggccctt tctggggcca cctccatcca 3240 cgaggagcag cctgagcctt ggtggccgaa ccttgaccgt cccggagcac agcttcaggg 3300 cagggaaccg gagcccctgg ggggcctcac gggtgtgacg aggcccttca ttgcaggcag 3360 gtgggccaat gggagccctc acccacgcaa gccgagacac cacccagagt gcaggctgcc 3420 tggccccttc tggcacggcc agctccacac cccctgccta gggtatgtgt ggtcctaagg 3480 gctaggagct tcccctacta acatctccca gaaaaagcag ttaagcccct cagggcacag 3540 caaggttaga cacagccccc atccccagat caggactcca tcttgctaag tggcatcacc 3600 gtcaccagcc tccccttatt taaaagcagc gactggtgtt gccgcaggta cctggtctac 3660 gaagacgcag gcatccctct cccaccgtcc acctccccgg gggccgctga cagcacagtc 3720 gcctgggtgc acgcttgtgg gggcagcagg aacggggctg tcggctctca ggggatctgg 3780 ctgcagccag ggcgagggcc tggcccttcc ttccagctcc ttccggctcc ttccagctga 3840 agggcaggaa gctctggccg cttagcttct agggttccat ctccctagaa aggtgcccac 3900 gcccagggca tcagtcagta gcggcagcag cagcagactc ggggctttcc cagggtggcg 3960 cagccacccc agctgcatgt cacctcagct ctccatctta ttgccatttt gtagatgagg 4020 aagctgagac cagaaaggct aagacccatg ccccaggcac cacacccatc tcttgggggc 4080 tgggcacctg ctacccgagg ccacctcctg aagcccccac tcttccccca tgttccactt 4140 caggagccgc gggggcccat cctgacaccc ggggttcctc agcccagcgc agatgtgctt 4200 cagttccaga gggcttgttg atttgtttct taggtacgtt acctgtccac cctgagtcca 4260 gtgaggctgt cccaagagcc cctgtagtgt gctcctggga agggctgggg gggctggggg 4320 ggctgggaga ggcccagggg cagctgtcac tggaacccca gccagatgtc caaggaagcc 4380 ggccagaaca cggagcagcc agatggcccc agctgcacct gtctagggag cccatgcagc 4440 ctccttgcac tggagaagca gctgtgaaag tagacagagt tgagacttcg ccgtggtcag 4500 gagaaaatgc aaattcccag gaacaagaat cctttaagtg atatgttttt ataaaactaa 4560 acaaatcaac aaataaatct tgaaggcgga tggttttccc agcagtgcag gggttggagg 4620 gaggctgctg gcactcctgg ggccaagggg gacaggcagt ggtcctgagt ctgctcagag 4680 aggcaaggca gaaggagctc gccaggcagg tcagctcaca tctgtccaag tcgctctggt 4740 cagaaacagc gactctcccc cattccccca gcgttcccac caggcctggg ctgctgggaa 4800 gcccttgctg tacccaggag cccgacccgc agtatcctgg cacagagcca cttgtcactc 4860 agaacagtca gtgtctccaa cgcacaaaca tccactcctc tgttaccagt taaagcactt 4920 taatgcttta aggtgaaaac gaaatcccat ccgtgttttt cgtgtaagat cgtgcttctc 4980 cgagcagtat taatggacgc cctccaatga cataacaact gtttttggta atgtaatctt 5040 gggaaaatgt gttatttttt tagctgtgtt tcagtgggga tttttgtttt tgtaacataa 5100 taaagtgtat gttccaatga aaaaaaaaaa a 5131 <210> 10 <211> 1395 <212> DNA <213> FANK 1 gene sequence of Homo sapiens <400> 10 cacttcgcct ccgggttgtc agggcaaccg tagcgacgcc ggccctggct gagaggcgtt 60 aggagtccgg gggttcgccc gcggaggccg gggagcagcc gaccatggag ccccagaaaa 120 tcatgccacc ctcaaagcct catccacctg tcgtgggcaa agtgactcat cacagcattg 180 aattatactg ggatctggaa aagaaagcca aacgccaagg acctcaagag cagtggttca 240 ggttctcgat tgaagaagaa gaccccaaaa tgcacactta tggtatcatt tatacgggat 300 atgcaacgaa gcatgttgtt gaaggtctgg aaccaaggac gctgtacaga tttcgcctga 360 aggtcaccag cccctctggg gagtgtgagt acagcccact cgtctcagtg tctacaacca 420 gagagcccat aagtagtgag cacttgcacc gggctgtcag tgtgaatgat gaagatttgc 480 tggtccgaat acttcaagga ggccgtgtta aggttgatgt tcccaataag tttggcttta 540 ccgctctgat ggttgctgcc cagaaaggat acaccaggct tgtgaaaatc ctagtttcta 600 atggcacaga cgtgaatctg aagaatggaa gtggcaagga cagtctaatg ctggcgtgct 660 atgcgggaca cctagatgtt gtgaaatatc tccgaagaca tggcgcttct tggcaggcta 720 gagacctggg aggctgtaca gctctgcact gggctgcaga tggaggccac tgcagtgtga 780 ttgagtggat gataaaggat ggctgtgagg tagacgtcgt ggacactggt tcaggatgga 840 ccccactcat gagagtctct gcggtgtcgg gaaatcagag ggtggcctct cttctaattg 900 atgctggggc caatgtgaat gtgaaggaca gaaatggaaa gacgcccctt atggtggctg 960 tgttaaataa tcatgaagag ttagttcagt tacttcttga caaaggggca gatgcaagtg 1020 taaaaaatga gttcggcaaa ggtgtcctag aaatggccag agtttttgac agacagagtg 1080 tagtctcctt attagaagaa aggaaaaaaa agcagaggcc aaagaagtct tgtgtctgct 1140 gatgagagca ccactcatct gcgaaacgca cgtaaaacaa agtgaaccgt gactgttaaa 1200 ctagggatgg gaaattctgc atcttggggg gctgtacatt tatttattta gttgaagatt 1260 cactgatccc actttgaaat acatcttttt acctaaaaaa aaaaaaaaaa aaaaaaaaaa 1320 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1380 aaaaaaaaaa aaaaa 1395 <210> 11 <211> 2095 <212> DNA <213> PPAPDC3 gene sequence of Homo sapiens <400> 11 aaatagccca ggcccgaggc agccaggccg cagctgtgga ctcctcacct cccggaggct 60 ctgctggtgc aggccccgca ttggagggct cgattggctg cccggctggc actgacgtcc 120 ccttggagct gggtggcaga ggagataaac agccatgtgc aactctccac actatattta 180 acagctgcgg cggagaaggc agggaggcag ccacggtggc ggctctgggg gcagctcttg 240 tcttcgggga gaaggccctt ggagccgggc tggcatcggc cttctcgggg tgagcgaggt 300 cccatgcca gcttcccaga gccgggcccg tgcccgggac cgcaacaacg tcctcaaccg 360 ggctgagttc ctgtccctga accagccccc caaggggggc ccggagcccc gcagctcggg 420 cagaaaggcc tcgggcccat cagcacagcc cccacctgct ggtgacgggg ccagagagcg 480 acgccagtca cagcagctgc cagaggagga ctgcatgcag ctgaacccct ccttcaaggg 540 catcgccttc aactccctgc tggccatcga tatctgtatg tccaagcggc tgggggtgtg 600 cgctggccgg gcggcgtcct gggccagtgc ccgctccatg gtcaagctca tcggcatcac 660 gggccacggc atcccctgga tcggaggcac catcctctgc ctggtgaaga gcagcacact 720 ggccggccag gaggtgctca tgaatctgct cctggccctg ctcctggaca tcatgacggt 780 ggccggcgtg cagaagctca tcaagcggcg cggcccgtac gagacgagcc ccagcctcct 840 ggactacctc accatggaca tctacgcctt cccggccggg cacgccagcc gcgccgccat 900 ggtgtccaag ttcttcctca gccacctggt gctggcggtg cccctgcgtg tgctgctggt 960 gctctgggcc ctctgcgtgg gcctgtcccg cgtgatgatc ggccgccacc acgtcacgga 1020 cgtcctctcc ggctttgtca tcggctacct ccagttccgt ctggtggagc tggtctggat 1080 gccctccagc acctgccaga tgctcatctc tgcctggtga agcgcccgcc ggcccacaca 1140 agcctctggg ggcagggctg gccctagaga aggggcaggg ggtggcgagg tggcgggcgt 1200 gggtggaaca gagcggccag gagtcagagc ggccaccccc acctcatctt cccctcctgg 1260 ctggaggctg gcgaacccag gccacccctc ccggagacaa gcgtgtttgg cagtgccagg 1320 cctcttgccc ctttgcttgg actccaagtc tcctctctag gcagccagga cccacccatg 1380 gggacagccc tatttagctt ctgctctggg aacagcaaaa atcaggatgg tgggaggggc 1440 cgagtcttgt cttgtccttt catcatcatg actgttgagt tcttggctgt gcccatcacg 1500 ccacagcacg acgcctgcca aaatgccccc aacctactgc ctgatgcagg tgccattgcc 1560 attagcggtc atcgacagct tagggcagca ctttccaacg ggtgcccatg ggacaccagc 1620 ctgcgagatg cttttggggg aaaggggttt tgtggttcaa taactttcgg aagtgctgca 1680 cactctgtcc ccaagttgga cattcacaaa ggccgttatt gccgtaaagg ctctgacaag 1740 ccctatagaa aagcttcttg ctaaaccttc tttaacccat gttttctaaa cttatttgac 1800 cacagaaccc ttttcttggg gaacagctat taacccccaa ggaattattg gttcctcaag 1860 tgcgttttgg gagctgctgc cagagagcta aagggcctgg ggtgtgagct gactctcctc 1920 tggggaggcc gggtgcacac gccacagccc gaggaaagtg ctggccaccg cccgtgggca 1980 tcgatgaggc tttggccccc aggggccgga ctccgtgtga cctaataggt cgtttccaag 2040 tcacccgttt tggatgtgca tttcatgtga caatacagat gacatgcaaa tggcc 2095

Claims (11)

(a) a gene selected from the group consisting of the TP73 gene represented by the nucleotide sequence of SEQ ID NO: 9, the FANK1 gene represented by the nucleotide sequence of SEQ ID NO: 10, and the PPAPDC3 gene represented by the nucleotide sequence of SEQ ID NO: 11 from the biological sample of the subject Measuring the expression level or methylation level of one gene; And
(b) comparing the expression level or methylation level of the gene measured in step (a) with an expression level or methylation level of the same gene in a normal control sample.
The method according to claim 1, wherein the expression level is measured by RT-PCR, competitive RT-PCR, real-time RT-PCR, RNase protection assay, Northern blotting, DNA microarray chip, Western blotting, enzyme-linked immunosorbent assay, radioimmunoassay (RIA), radial immunodiffusion, Ouchteroni Wherein the method is selected from the group consisting of immunodiffusion, rocket immunoelectrophoresis, immunohistochemistry, immunoprecipitation, complement fixation, flow cytometry (FACS) and protein chip methods.
The method according to claim 1, wherein the methylation level is measured by MIRA (methylated-CpG island recovery assay), PCR, methylation specific PCR, real time methylation specific PCR, Characterized in that it is measured by at least one method selected from the group consisting of PCR using an antigen binding protein, quantitative PCR, pyrosequencing and bisulfite sequencing.
2. The method of claim 1, wherein the biological sample is at least one selected from the group consisting of blood, urine, cells and tissues.
5. The method of claim 4, wherein the cell is a CD4 ⁺ T cell.
The method according to claim 1, wherein the method further comprises the step of measuring an expression level or a methylation level of at least one gene selected from the group consisting of the following genes:
GenBank Accession No. NM_019102), TPTE (GenBank Accession No. NM_199260), SPESP1 (GenBank Accession No. NM_145658), MIR200A (GenBank Accession No. NR_029834), NADK (GenBank Accession No. NM_001198995), LOC100130417 , GenBank Accession No. NR_026074), MIR663B (GenBank Accession No. NR_031608), ANKRD30BL (GenBank Accession No. NR_027020), UCN (GenBank Accession No. NM_003353), LOC100130872 (GenBank Accession No. NR_024569), SPON2 (GenBank Accession No. NM_001199021), MIR1229 (GenBank Accession No. NR_031598), C6orf201 (GenBank Accession No. NM_001085401), MEST (GenBank Accession No. NM_002402), SOHLH1 (GenBank Accession No. NM_001101677), SYCE1 (GenBank Accession No. NM_001143763), ANKRD30A (GenBank Accession No. GenBank Accession No. NM_001209974), REREP3 (GenBank Accession No. NM_001109997), GenBank Accession No. NM_001109998, GenBank Accession No. NM_0299997), KCNQ1DN (GenBank Accession No. NR_024627), AGAP2 (GenBank Accession No. NM_001122772), TDRD9 (GenBank Accession No. NM_153046), FAM181A GenBank Accession No. NR_033735), NOX5 (GenBank Accession No. GenBank Accession No. NR_038678), ALOX12 (GenBank Accession No. NM_000697), MIR3187 (GenBank Accession No. NR_036154), LOC100288123 (GenBank Accession No. NR_034114), EXOC3L2 (GenBank Accession No. NM_138568), MIR4745 GenBank Accession No. NR_039900), C19orf77 (GenBank Accession No. NM_001136503), C19orf34 (GenBank Accession No. NR_033400), MIR663 (GenBank Accession No. NR_030386), C20orf177 (GenBank Accession No. NM_001190826), GNAS (GenBank Accession No. NR_003259 ), TP73 (GenBank Accession No. NM_001126240), TTLL10 (GenBank Accession No. NM_153254), FAM132A (GenBank Accession No. NM_001014980), C1orf146 (GenBank Accession No. NM_001012425), EIF2B3 (GenBank Accession No. NM_020365), CCDC27 Accession No. NM_152492), CROCCL1 (GenBank Accession No. NR_026752), FAM58B (GenBank Accession No. NM_001105517), TMEM61 (GenBank Accession No. NM_182532), OBSCN (GenBank Accession No. NM_052843), OBSCN (GenBank Accession No. NM_001098623) , GPR25 (GenBank Accession No. NM_005298), C1orf17 0 (GenBank Accession No. &lt; / RTI &gt; , GenBank Accession No. NM_005248), HSPA7 (GenBank Accession No. NR_024151), PER3 (GenBank Accession No. NM_016831), CLDN19 (GenBank Accession No. NM_001123395), MMEL1 (GenBank Accession No. NM_033467), PLEKHN1 GenBank Accession No. NM_032129), GPR37L1 (GenBank Accession No. NM_004767), SLC25A44 (GenBank Accession No. NM_014655), ICMT (GenBank Accession No. NM_012405), KLF17 (GenBank Accession No. NM_173484), AFARP1 ), HIST3H3 (GenBank Accession No. NM_003493), OR2L13 (GenBank Accession No. NM_175911), PVRL4 (GenBank Accession No. NM_030916), EPS8L3 (GenBank Accession No. NM_139053), CLCNKA (GenBank Accession No. NM_004070), NCRNA00164 Accession No. NR_027020), UCN (GenBank Accession No. NM_003353), KRTCAP3 (GenBank Accession No. NM_173853), NCRNA00164 (GenBank Accession No. NR_027019), ANKMY1 (GenBank Accession No. NM_016552), TEKT4 (GenBank Accession No. NM_144705) , LOC654433 (GenBank Accession No. NR_015377), DNAJC5G (GenBank Accession No. NM_173650) , C2OF54 (GenBank Accession No. GenBank Accession No. NM_031313), KLHL30 (GenBank Accession No. NM_198582), POTEF (GenBank Accession No. NM_001099771), BOLL (GenBank Accession No. NM_033030), RGPD4 (GenBank Accession No. NM_182588), TUBA3D GenBank Accession No. NM_080386), ARHGEF4 (GenBank Accession No. NM_032995), RGPD3 (GenBank Accession No. NM_001144013), CRYGA (GenBank Accession No. NM_014617), PRLH (GenBank Accession No. NM_015893), LOC401010 (GenBank Accession No. NR_002826 ), MFSD2B (GenBank Accession No. NM_001080473), EMILIN1 (GenBank Accession No. NM_007046), SCTR (GenBank Accession No. NM_002980), C2orf39 (GenBank Accession No. NM_145038), NT5DC2 (GenBank Accession No. NM_022908), PRR23C Accession No. NM_001134657), ITIH4 (GenBank Accession No. NM_002218), DPPA2 (GenBank Accession No. NM_138815), RARRES1 (GenBank Accession No. NM_206963), GRK7 (GenBank Accession No. NM_139209), TM4SF19 (GenBank Accession No. NM_138461) , OSTalpha (GenBank Accession No. NM_152672), AMT (GenBank Accession No. NM_00048 1), PRSS50 (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_001134659), SLC6A11 (GenBank Accession No. NM_001134659), and GenBank Accession No. NM_023251) GenBank Accession No. NM_014229), PRSS42 (GenBank Accession No. NM_182702), LOC100130872 (GenBank Accession No. NR_024569), DCAF4L1 (GenBank Accession No. NM_001029955), C4orf44 (GenBank Accession No. NM_001042690), TRIM60 ), FAM92A3 (GenBank Accession No. NR_003612), ADAD1 (GenBank Accession No. NM_139243), RBM46 (GenBank Accession No. NM_144979), OTOP1 (GenBank Accession No. NM_177998), SLC26A1 (GenBank Accession No. NM_213613), RNF212 Accession No. NM_001131034), LOC650293 (GenBank Accession No. NM_001040071), ZNF595 (GenBank Accession No. NM_182524), FRG1 (GenBank Accession No. NM_004477), YTHDC1 (GenBank Accession No. NM_001031732), NAP1L5 (GenBank Accession No. NM_153757) , COX7B2 (GenBank Accession No. NM_130902), FTMT (GenBank Accessio n No. (GenBank Accession No. NM_001080478), SLC25A2 (GenBank Accession No. NM_031947), CMYA5 (GenBank Accession No. NM_153610), SLC6A19 (GenBank Accession No. NM_001003841), IL3 (GenBank Accession No. NM_000588), C5orf47 GenBank Accession No. NM_001144954), DND1 (GenBank Accession No. NM_194249), CDX1 (GenBank Accession No. NM_001804), SLC45A2 (GenBank Accession No. NM_016180), CDH9 (GenBank Accession No. NM_016279), FAM170A (GenBank Accession No. NM_182761 ), PDLIM4 (GenBank Accession No. NM_003687), PFN3 (GenBank Accession No. NM_001029886), ZDHHC11 (GenBank Accession No. NM_024786), LOC134466 (GenBank Accession No. NR_026867), PPP1R2P3 (GenBank Accession No. NR_002168), GMCL1L Accession No. NR_003281), PLEKHG4B (GenBank Accession No. NM_052909), IRX2 (GenBank Accession No. NM_033267), C6orf201 (GenBank Accession No. NM_001085401), HIST1H1A (GenBank Accession No. NM_005325), DUSP22 (GenBank Accession No. NM_020185) , HDGFL1 (GenBank Accession No. NM_138574), DDX43 (GenBank Accession No . (GenBank Accession No. NM_007471), HIST1H4G (GenBank Accession No. NM_003547), DPPA5 (GenBank Accession No. NM_001025290), FAM50B (GenBank Accession No. NM_012135), FRMD1 (GenBank Accession No. NM_024919), PNLDC1 GenBank Accession No. NM_171616), TDRD6 (GenBank Accession No. NM_001010870), HUS1B (GenBank Accession No. NM_148959), ID4 (GenBank Accession No. NM_001546), MCART3P (GenBank Accession No. NR_026540), C6orf221 (GenBank Accession No. NM_001017361 GenBank Accession No. NM_002402), BHLHA15 (GenBank Accession No. NM_177455), NOBOX (GenBank Accession No. NM_001080413), HOXA4 (GenBank Accession No. NM_002141), GPR146 (GenBank Accession No. NM_138445), ZNF716 Accession No. NM_001159279), RAMP3 (GenBank Accession No. NM_005856), AMZ1 (GenBank Accession No. NM_133463), SGCE (GenBank Accession No. NM_001099401), ELFN1 (GenBank Accession No. NM_001128636), CPA1 (GenBank Accession No. NM_001868) , AMAC1L2 (GenBank Accession No. NM_054028), TSPYL5 (GenBank Accession No. NM_0335 12), KIAA1875 (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_032611), PSTEA (GenBank Accession No. NM_032611), and CSMD3 (GenBank Accession No. NM_032611). GenBank Accession No. NM_198124), NRBP2 (GenBank Accession No. NM_178564), LOC100130274 (GenBank Accession No. NM_001162914), C8orf73 (GenBank Accession No. NM_001100878), GPIHBP1 (GenBank Accession No. NM_178172), LY6D ), GPT (GenBank Accession No. NM_005309), MAPK15 (GenBank Accession No. NM_139021), LRRC24 (GenBank Accession No. NM_001024678), RP1L1 (GenBank Accession No. NM_178857), SLC45A4 (GenBank Accession No. NM_001080431), SNX16 Accession No. NM_022133), SOHLH1 (GenBank Accession No. NM_001012415), EGFL7 (GenBank Accession No. NM_016215), PTGDS (GenBank Accession No. NM_000954), NPR2 (GenBank Accession No. NM_003995) , NR5A1 (GenBank Accession No. NM_004959), FAM166A (GenBank Accession No. NM_00 1001710), C9orf135 (GenBank Accession No. &lt; / RTI &gt; GenBank Accession No. NM_001136113, GenBank Accession No. NM_001136113), TMC1 (GenBank Accession No. NM_001136113), MAMDC4 (GenBank Accession No. NM_001136113), CARD9 (GenBank Accession No. NM_052813), OR13J1 (GenBank Accession No. NM_001004487), C9orf152 GenBank Accession No. NM_138691), CACNA1B (GenBank Accession No. NM_000718), PRKACG (GenBank Accession No. NM_002732), PAEP (GenBank Accession No. NM_001018049), S1PR3 (GenBank Accession No. NM_005226), SNORD62A , GenBank Accession No. NM_052997), C10orf116 (GenBank Accession No. NM_006829), GPR26 (GenBank Accession No. NM_153442), CTBP2 (GenBank Accession No. NM_022802), CCNY (GenBank Accession No. NM_181698), PNLIPRP2 Accession No. NM_005396), PYROXD2 (GenBank Accession No. NM_032709), GDF2 (GenBank Accession No. NM_016204), MMP21 (GenBank Accession No. NM_147191), CALML3 (GenBank Accession No. NM_005185), JAKMIP3 (GenBank Accession No. NM_001105521) , ANKRD2 (GenBank Accession No. NM_020349), C10orf108 (GenBank Accession No. (GenBank Accession No. NM_033261), RBP3 (GenBank Accession No. NM_002900), TUBB8 (GenBank Accession No. NM_177987), TUBGCP2 (GenBank Accession No. NM_006659), KCNQ1DN (GenBank Accession No. NR_024627), LOC441601 GenBank Accession No. NR_003034), SPDYC (GenBank Accession No. NM_001008778), CD248 (GenBank Accession No. NM_020404), TSSC4 (GenBank Accession No. NM_005706), H19 (GenBank Accession No. NR_002196), LDHAL6A (GenBank Accession No. NM_144972 ), FOXR1 (GenBank Accession No. NM_181721), PKP3 (GenBank Accession No. NM_007183), MS4A15 (GenBank Accession No. NM_001098835), MRGPRE (GenBank Accession No. NM_001039165), MUC6 (GenBank Accession No. NM_005961), LSP1 Accession No. NM_002339), TNNT3 (GenBank Accession No. NM_006757), TP53AIP1 (GenBank Accession No. NM_022112), CATSPER1 (GenBank Accession No. NM_053054), TAGLN (GenBank Accession No. NM_001001522), CABP2 (GenBank Accession No. NM_016366) , GNG3 (GenBank Accession No. NM_012202), CEND1 (GenBank Accession No. NM_016564), FOLR3 GenBank Accession No. GenBank Accession No. NM_0005975), GenBank Accession No. NM_005995), SCGB2A1 (GenBank Accession No. NM_002407), C11orf36 (GenBank Accession No. NR_027138), DRD4 (GenBank Accession No. NM_000797), MUC2 GenBank Accession No. NM_002457), AGAP2 (GenBank Accession No. NM_001122772), RPL13AP20 (GenBank Accession No. NR_003932), FIGNL2 (GenBank Accession No. NM_001013690), ACRBP (GenBank Accession No. NM_032489), SLC6A12 ), KRT3 (GenBank Accession No. NM_057088), TUBGCP3 (GenBank Accession No. NM_006322), SOHLH2 (GenBank Accession No. NM_017826), ATP4B (GenBank Accession No. NM_000705), RNF17 (GenBank Accession No. NM_031277), TUBA3C Accession No. NM_006001), CSNK1A1L (GenBank Accession No. NM_145203), DLEU7 (GenBank Accession No. NM_198989), TDRD9 (GenBank Accession No. NM_153046), DIO3 (GenBank Accession No. NM_001362), COX8C (GenBank Accession No. NM_182971) , ASPG (GenBank Accession No. NM_001080464), MGC23270 (GenBank Accession No. NR_024396 ), RPL13AP3 (GenBank Accession No. GenBank Accession No. NM_031464), ACOT4 (GenBank Accession No. NM_152331), CMTM5 (GenBank Accession No. NM_138460), INF2 (GenBank Accession No. NM_022489), AMN (GenBank Accession No. NM_030943), ABHD12B GenBank Accession No. NM_181533), TBPL2 (GenBank Accession No. NM_199047), PSMB11 (GenBank Accession No. NM_001099780), CATSPER2 (GenBank Accession No. NM_054020), LOC390594 (GenBank Accession No. NM_001101362), C15orf2 (GenBank Accession No. NM_018958 GenBank Accession No. NR_003309, GenBank Accession No. NR_003309), RASL12 (GenBank Accession No. NM_016563), GenBank Accession No. NM_0016563, , SNORD115-32 (GenBank Accession No. NR_003347), SNORD115-31 (GenBank Accession No. NR_003346), LASS3 (GenBank Accession No. NM_178842), SNORD115-37 (GenBank Accession No. NR_003352), LDHAL6B (GenBank Accession No. NM_033195 ), GABRB3 (GenBank Accession No. NM_000814), SNORD115-25 (GenBank Accession No. NR_003342), SLC28A 2 (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_0021212), ZNF469 (GenBank Accession No. NM_001127464), CCDC154 (GenBank Accession No. NM_001143980), TESSP1 (GenBank Accession No. NM_001135086), ELMO3 (GenBank Accession No. NM_024712), ZSCAN10 GenBank Accession No. NM_006849), LOC146336 (GenBank Accession No. NR_027242), CLDN9 (GenBank Accession No. NM_020982), CLDN6 (GenBank Accession No. NM_021195), IGFALS (GenBank Accession No. NM_001146006), IL34 (GenBank Accession No. NM_152456 , GenBank Accession No. NM_001083601), SSTR5 (GenBank Accession No. NM_001053), DNASE1L2 (GenBank Accession No. NM_001374), MSLN (GenBank Accession No. NM_005823), CMTM1 (GenBank Accession No. NM_052999), FBRS Accession No. NM_001105079), ZNF597 (GenBank Accession No. NM_152457), SLC5A11 (GenBank Accession No. NM_052944), IL17C (GenBank Accession No. NM_013278), FAM18A (GenBank Accession No. NM_001079512), TPSG1 (GenBank Accession No. NM_012467) , GPR97 (GenBank Accession No. NM_170776), PRM2 (GenBank Accession No. NM_00 2762), JMJD8 (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_139174), C16orf81 (GenBank Accession No. NR_024347), TPSD1 (GenBank Accession No. NM_012217), ADCY7 (GenBank Accession No. NM_001114), ZG16B (GenBank Accession No. NM_145252), CHST5 GenBank Accession No. NM_024533), PRR25 (GenBank Accession No. NM_001013638), ABCA3 (GenBank Accession No. NM_001089), CCDC79 (GenBank Accession No. NM_001136505), WDR59 (GenBank Accession No. NM_030581), GLIS2 (GenBank Accession No. NM_032575 ), MT1L (GenBank Accession No. NR_001447), TMPRSS8 (GenBank Accession No. NR_026864), TMC7 (GenBank Accession No. NM_024847), DNASE1 (GenBank Accession No. NM_005223), ALOX12 (GenBank Accession No. NM_000697), KCNAB3 Accession No. NM_004732), DYSFIP1 (GenBank Accession No. NM_001007533), QRICH2 (GenBank Accession No. NM_032134), FSCN2 (GenBank Accession No. NM_012418), CACNG1 (GenBank Accession No. NM_000727), TMEM88 (GenBank Accession No. NM_203411) , UTS2R (GenBank Accession No. NM_018949), HSPB9 (GenBank Accession No. NM_033194), NLGN 2 (GenBank Accession No. &lt; / RTI &gt; GenBank Accession No. NR_026718), FLJ36000 (GenBank Accession No. NR_027084), RPH3AL (GenBank Accession No. NM_006987), GGT6 (GenBank Accession No. NM_001122890), RAB34 (GenBank Accession No. NM_031934), SHISA6 GenBank Accession No. NM_207386), GPR172B (GenBank Accession No. NM_001104577), SLFN13 (GenBank Accession No. NM_144682), HSF5 (GenBank Accession No. NM_001080439), ENPP7 (GenBank Accession No. NM_178543), AIPL1 (GenBank Accession No. NM_014336 ), AMAC1 (GenBank Accession No. NM_152462), KCTD11 (GenBank Accession No. NM_001002914), WSB1 (GenBank Accession No. NM_015626), SERPINF1 (GenBank Accession No. NM_002615), ULK2 (GenBank Accession No. NM_014683), TBX4 Accession No. NM_018488), CCDC144NL (GenBank Accession No. NM_001004306), KCNG2 (GenBank Accession No. NM_012283), RNF138 (GenBank Accession No. NM_016271), ANKRD30B (GenBank Accession No. NM_001145029), PSMA8 (GenBank Accession No. NM_144662) , CNDP1 (GenBank Accession No. NM_032649), EXOC3L2 (GenBank Accession No. NM_1 38568), C19orf77 (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_031310), YJEFN3 (GenBank Accession No. NM_031310), GenBank Accession No. NM_031310, GenBank Accession No. NM_031310) GenBank Accession No. NM_198537), CCDC155 (GenBank Accession No. NM_144688), TMEM86B (GenBank Accession No. NM_173804), SPACA4 (GenBank Accession No. NM_133498), PRR22 (GenBank Accession No. NM_001134316), ELANE ), ACPT (GenBank Accession No. NM_033068), PSPN (GenBank Accession No. NM_004158), WDR88 (GenBank Accession No. NM_173479), PLIN4 (GenBank Accession No. NM_001080400), OR10H1 (GenBank Accession No. NM_013940), CCDC105 Accession No. NM_173482), SNORD37 (GenBank Accession No. NR_002602), DUS3L (GenBank Accession No. NM_020175), CBLC (GenBank Accession No. NM_012116), LGALS4 (GenBank Accession No. NM_006149), COX7A1 (GenBank Accession No. NM_001864) , KCNA7 (GenBank Accession No. NM_031886), NTN5 (GenBank Accession No. NM_145807), SN ORD35A (GenBank Accession No. &lt; / RTI &gt; GenBank Accession No. NM_005306), ZSCAN1 (GenBank Accession No. NM_182572), LOC126536 (GenBank Accession No. NR_026828), LYPD4 (GenBank Accession No. NM_173506), DMRTC2 (GenBank Accession No. NM_001040283), ACTL9 GenBank Accession No. NM_178525), TDRD12 (GenBank Accession No. NM_001110822), CAPS (GenBank Accession No. NM_004058), PGLYRP1 (GenBank Accession No. NM_005091), CAPN12 (GenBank Accession No. NM_144691), FAM83E (GenBank Accession No. NM_017708 ), NLRP4 (GenBank Accession No. NM_134444), PPAP2C (GenBank Accession No. NM_003712), UPK1A (GenBank Accession No. NM_007000), INSL3 (GenBank Accession No. NM_005543), KCNJ14 (GenBank Accession No. NM_170720), ODF3L2 Accession No. NM_182577), PLK5P (GenBank Accession No. NR_026557), AURKC (GenBank Accession No. NM_001015878), ECH1 (GenBank Accession No. NM_001398), SRMS (GenBank Accession No. NM_080823), FRG1B (GenBank Accession No. NR_003579) , SSTR4 (GenBank Accession No. NM_001052), SLC12A5 (GenBank Accession No. NM_020708), L3MBTL (GenBank Accession No. 2). (GenBank Accession No. NM_032609), CTCFL (GenBank Accession No. NM_080618), SALL4 (GenBank Accession No. NM_032107), TCEA2 (GenBank Accession No. NM_198723), FAM83C (GenBank Accession No. NM_178468), PHF20 (GenBank Accession No. NM_016436), COX4I2 GenBank Accession No. NM_020436), SLC13A3 (GenBank Accession No. NM_022829), MYL9 (GenBank Accession No. NM_006097), ADRA1D (GenBank Accession No. NM_000678), RTEL1 (GenBank Accession No. NM_032957), BIRC7 (GenBank Accession No. NM_139317 ), AIRE (GenBank Accession No. NM_000383), TFF1 (GenBank Accession No. NM_003225), KRTAP10-6 (GenBank Accession No. NM_198688), FTCD (GenBank Accession No. NM_006657), IGSF5 (GenBank Accession No. NM_001080444) (GenBank Accession No. NM_174981), PLAC4 (GenBank Accession No. NM_182832), SNORA80 (GenBank Accession No. NR_002996), MOV10L1 (GenBank Accession No. NM_018995), HORMAD2 (GenBank Accession No. NM_152510), LOC400931 (GenBank Accession No. CAMNA1I (GenBank Accession No. NM_021096), TMEM211 (GenBank Accession No. NM_001001663), BAI AP2L2 (GenBank Accession No. &lt; / RTI &gt; GenBank Accession No. NM_005297), SUSD2 (GenBank Accession No. NM_019601), GGT1 (GenBank Accession No. NM_005265), RFPL2 (GenBank Accession No. NM_001098527), MCHR1 (GenBank Accession No. NM_005297), MAPK8IP2 GenBank Accession No. NM_012324), CHADL (GenBank Accession No. NM_138481), RGL4 (GenBank Accession No. NM_153615), TCF20 (GenBank Accession No. NM_005650), OTUD6A (GenBank Accession No. NM_207320), FAM9A (GenBank Accession No. NM_174951 GenBank Accession No. NM_001031834), CT45A1 (GenBank Accession No. NM_001017417), GJB1 (GenBank Accession No. NM_000166), YY2 (GenBank Accession No. NM_206923), FAM9B (GenBank Accession No. NM_205849)
The expression level of any one gene selected from the group consisting of the TP73 gene represented by the nucleotide sequence of SEQ ID NO: 9, the FANK1 gene represented by the nucleotide sequence of SEQ ID NO: 10, and the PPAPDC3 gene represented by the nucleotide sequence of SEQ ID NO: A composition for the diagnosis of psoriasis comprising an agent for measuring the level.
8. The primer according to claim 7, wherein the agent for measuring the expression level of the gene specifically binds to the gene. A probe and an antibody specifically recognizing the expression protein of the gene.
9. The primer of claim 8, wherein the primer is any one or more primer pairs selected from the group consisting of primer pairs of SEQ ID NOS: 1 and 2, primer pairs of SEQ ID NOS: 3 and 4, and primer pairs of SEQ ID NOS: 5 and 6 Composition for the diagnosis of psoriasis.
8. The method according to claim 7, wherein the agent for measuring the methylation level is selected from the group consisting of a compound or a methylation-sensitive restriction enzyme that modifies an unmethylated cytosine base, a primer specific to the methylated sequence of the gene, and a primer specific to the unmethylated sequence Or a pharmaceutically acceptable salt thereof.
A TP73 gene represented by the nucleotide sequence of SEQ ID NO: 9, a FANK1 gene represented by the nucleotide sequence of SEQ ID NO: 10, and a PPAPDC3 gene represented by the nucleotide sequence of SEQ ID NO: 11 or a methylation level Wherein the composition is administered to a patient.

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