KR101562050B1 - Composition for diagnosing psoriasis - Google Patents

Abstract

More particularly, the present invention relates to a method for detecting methylation of a promoter of a gene located on the X chromosome to provide information necessary for the diagnosis of psoriasis, and a method for detecting the methylation level of the gene promoter The present invention relates to a composition for the diagnosis of psoriasis. The methods and compositions of the present invention are useful in the diagnosis of psoriasis because they can provide genetic information in the diagnosis of psoriasis skin disease.

Description

Composition for diagnosing psoriasis {Composition for diagnosing psoriasis}

The present invention relates to the detection of the methylation level of a gene promoter showing a tendency for psoriasis-specific methylation, and more particularly, a method of detecting methylation of a promoter of a gene located on the X chromosome to provide information necessary for the diagnosis of psoriasis, and measuring the methylation level. It relates to a composition for diagnosis of psoriasis comprising an agent capable of.

DNA methylation is one of the mechanisms for regulating gene expression. It is one of the mechanisms for suppressing gene expression by lowering the reactivity and increasing stability of DNA by substituting the DNA sequence with methyl group. DNA is not methylated when it is first replicated, but it is methylated after replication. DNA methylation causes inactivation of a gene without a change in the DNA sequence, and is classified as an epigenetic change, distinguishing it from genetic changes such as point mutations and gene deletions.

Recently, methods for diagnosing cancer through DNA methylation measurement have been proposed, and DNA methylation occurs mainly in the cytosine of CpG island at the promoter region of a specific gene, and thereby the binding of transcription factors is disturbed. As a result, the transcription of a specific gene is blocked. Searching the methylation of the promoter CpG island of the tumor suppressor gene is of great help in cancer research. Attempts to be used for diagnosis and screening of cancer by testing by methods such as base analysis have been actively made.

This is controversial as to whether methylation of the promoter CpG island directly induces carcinogenesis or whether it is a secondary change in carcinogenesis, but in many cancers, a tumor suppressor gene, a DNA repair gene, and a cell cycle It was confirmed that the expression of these genes was blocked due to hyper-methylation of regulatory genes and the like, and it was found that hypermethylation occurs at the promoter region of a specific gene, especially in the early stages of cancer development. Therefore, promoter methylation of tumor-related genes is recognized as an important indicator of cancer, and attempts to be used in various cancer treatments by investigating the promoter methylation of tumor-related genes in actual blood, sputum, saliva, feces, and urine have recently been actively made. (Esteller, M. et al., Cancer Res., 59:67, 1999; Sanchez-Cespedez, M. et al., Cancer Res., 60:892, 2000; Ahlquist, DA et al., Gastroenterol., 119:1219, 2000). However, the methylation of promoters of genes related to other diseases has not been studied. In particular, no studies have been conducted on gene promoters that specifically exhibit methylation in psoriasis patients or their application.

Psoriasis is one of the chronic inflammatory diseases that occur in the skin and is characterized by the formation of thick, scaly stratum corneum. The etiology of psoriasis has not been clearly elucidated, but various evidences suggest that cytokines released from activated T cells are T-cell mediated inflammatory diseases that promote the proliferation of keratinocytes. (Prinz, JC et al., 1997 and Chang, JCC et al., 1994).

In addition, studies have shown that genetic factors are involved in the occurrence of psoriasis. About a third of patients have a family history, and identical twins are more than three times more likely to develop psoriasis than fraternal twins. It is also supported that the probability of developing psoriasis within the family is also proportional to the relatedness (Wuepper et al., J. Invest. Dermatol., 95: 2S-4S 1990).

Currently, the treatment of psoriasis is an ointment that temporarily relieves symptoms or a prescription that induces continuous skin care, and there is no fundamental treatment in practice. Considering the side effects of treatments for psoriasis skin diseases, including steroids, it is necessary to develop a method that can fundamentally treat these diseases without side effects, and genetic targets and diagnostic methods for this need to be developed.

Accordingly, as a result of researching a new method of diagnosis of psoriasis, the present inventors completed the present invention by confirming that the methylation level of the promoters of the gene located on the X chromosome was significantly higher than that of the control group in which psoriasis patients were normal.

Accordingly, an object of the present invention is to provide information necessary for the diagnosis of psoriasis by (a) measuring the methylation level of a promoter of a gene located on the X chromosome from a target sample; And (b) comparing the methylation level of the promoter with the methylation level of the same promoter in the normal control sample.

Another object of the present invention is to provide a composition for diagnosing psoriasis comprising an agent for measuring the methylation level of a promoter of a gene located on the X chromosome.

Another object of the present invention is to provide a kit for diagnosing psoriasis comprising an agent for measuring the methylation level of a promoter of a gene located on the X chromosome.

In order to achieve the above object, the present invention provides information necessary for the diagnosis of psoriasis, comprising the steps of: (a) measuring the methylation level of a promoter of a gene located on the X chromosome from a target sample; And (b) comparing the methylation level of the promoter with the methylation level of the same promoter in the normal control sample.

In order to achieve another object of the present invention, the present invention provides a composition for diagnosing psoriasis comprising an agent for measuring the methylation level of a promoter of a gene located on the X chromosome.

In order to achieve another object of the present invention, the present invention provides a kit for diagnosing psoriasis comprising an agent for measuring the methylation level of a promoter of a gene located on the X chromosome.

Hereinafter, the present invention will be described in detail.

In order to provide information necessary for the diagnosis of psoriasis, the present invention comprises the steps of: (a) measuring the methylation level of a promoter of a gene located on the X chromosome from a target sample; And (b) comparing the methylation level of the promoter with the methylation level of the same promoter in the normal control sample.

Methylation of a promoter of a gene causes inactivation of a gene without a change in the DNA sequence, and is classified as an epigenetic change, distinguishing it from genetic changes such as point mutations and gene deletions. Changes in methylation levels include both hypermethylation and hypomethylation. The change in methylation level is mainly studied in relation to cancer, and there is no known information about the measurement of the change in methylation level related to psoriasis.

Diagnosis refers to confirming the presence or characteristics of a pathological condition, and diagnosis of the present invention refers to confirming the onset of psoriasis.

The target sample may be any sample capable of separating the gene of the measurement target, and the target sample is preferably at least one selected from the group consisting of tissues, cells, blood, and urine derived from a suspected psoriasis patient or a diagnosis target. Can be.

The cell may be any cell capable of separating the gene to be measured, but may preferably be a naive T cell.

The methylation level measurement may be performed by a known method for measuring the methylation level of nucleic acids, for example, MIRA (methylated-CpG island recovery assay), PCR, methylation specific PCR, and real-time methylation specific PCR. time methylation specific PCR), PCR using a methylated DNA-specific binding protein, quantitative PCR, pyrosequencing, and bisulfite sequencing, and may be one or more methods selected from the group consisting of, preferably MIRA (methylated-CpG island recovery assay). ) Can be.

The average methylation level of the promoter of the gene located on the X chromosome of psoriasis patients is specifically higher than that of the normal control group, and this point is disclosed for the first time in the present invention.

Genes located on the X chromosome of the present invention are preferably LOC339822 (GenBank Accession No. NR_033880), FKBP6 (GenBank Accession No. NM_003602), TRIM50 (GenBank Accession No. NM_178125), ABCD1 (GenBank Accession No. NM_000033), EMD ( GenBank Accession No. NM_000117), HPRT1 (GenBank Accession No. NM_000194), PHKA2 (GenBank Accession No. NM_000292), G6PD (GenBank Accession No. NM_000402), NR0B1 (GenBank Accession No. NM_000475), RPL39 (GenBank Accession No. NM_000475), RPL39 (GenBank Accession No. NM_000475) ), MAP3K15 (GenBank Accession No. NM_001001671), ZDHHC9 (GenBank Accession No. NM_001008222), KIAA2022 (GenBank Accession No. NM_001008537), DNASE1L1 (GenBank Accession No. NM_001009934), ZMAT1 (GenBank Accession No. NM_001009934), ZMAT1 (GenBank Accession No. NM_001009934), ZMAT1 (GenBank Accession No. Accession No. NM_001013627), DCAF12L2 (GenBank Accession No. NM_001013628), CXorf40B (GenBank Accession No. NM_001013845), VMA21 (GenBank Accession No. NM_001017980), RGAG4 (GenBank Accession No.18RF55 (GenBank Accession No.18 NM_001024455), LON , SCML1 (GenBank Accession No. NM_001037540), PRPS2 (GenBank Accession No. NM_001039 091), GPRASP1 (GenBank Accession No. NM_001099411), MAGIX (GenBank Accession No. NM_001099680), ANKRD58 (GenBank Accession No. NM_001105576), MECP2 (GenBank Accession No. NM_001110792), CASK (GenBank Accession No. NM_001126054), ELF4 (GenBank Accession No. NM_001126054), ELF4 (GenBank Accession No. GenBank Accession No. NM_001127899), FAM58A (GenBank Accession No. NM_001130997), FAM127B (GenBank Accession No. NM_001134321), PNCK (GenBank Accession No. NM_001135740), NDUFB11 (GenBank Accession No. ), BCAP31 (GenBank Accession No. NM_001139441), PDK3 (GenBank Accession No. NM_001142386), DKC1 (GenBank Accession No. NM_001142463), IKBKG (GenBank Accession No. NM_001145255), FHL1 (GenBank Accession No. NM_001159703), FAM104 Accession No. NM_001166704), MAP7D2 (GenBank Accession No. NM_001168465), CNKSR2 (GenBank Accession No. NM_001168649), AFF2 (GenBank Accession No. NM_001169124), CXorf58 (GenBank Accession No. NM_001_170704), MBNL3ank Accession No. NM_001_169574), MBNL , SRPX (GenBank Accession No. NM_00 1170750), CXorf40A (GenBank Accession No. NM_001171908), TMEM185A (GenBank Accession No. NM_001174092), MAMLD1 (GenBank Accession No. NM_001177465), PPP1R3F (GenBank Accession No. NM_001184745), SLITRK No. GenBank Accession No. NM_001193270), RBM10 (GenBank Accession No. NM_001204467), DUSP9 (GenBank Accession No. NM_001395), GPC4 (GenBank Accession No. NM_001448), GDI1 (GenBank Accession No. NM_001493560), IL13RA1493560 ), IRAK1 (GenBank Accession No. NM_001569), SHROOM2 (GenBank Accession No. NM_001649), MPP1 (GenBank Accession No. NM_002436), SUV39H1 (GenBank Accession No. NM_003173), ZIC3 (GenBank Accession No. NM_003413) Accession No. NM_003604), FGF13 (GenBank Accession No. NM_004114), IDH3G (GenBank Accession No. NM_004135), NDUFA1 (GenBank Accession No. NM_004541), RPS6KA3 (GenBank Accession No. NM_004586), RAB33A (GenBank Accession No. NM_004586), RAB33A. , HMGB3 (GenBank Accession No. NM_005342), SOX3 (GenBank Accession No. NM_005 634), PQBP1 (GenBank Accession No. NM_005710), RPL10 (GenBank Accession No. NM_006013), HDAC6 (GenBank Accession No. NM_006044), PRICKLE3 (GenBank Accession No. NM_006150), SSR4 (GenBank Accession No. NM_006280), SLC16A2 (GenBank Accession No. NM_006517), TFE3517 GenBank Accession No. NM_006521), RBM3 (GenBank Accession No. NM_006743), RNF113A (GenBank Accession No. NM_006978), WDR45 (GenBank Accession No. NM_007075), ZNF41 (GenBank Accession No. NM_007130), FTSJ1 (GenBank Accession No. NM_007130), FTSJ1 (GenBank Accession No. NM_007130). ), PNMA3 (GenBank Accession No. NM_013364), UBL4A (GenBank Accession No. NM_014235), RPS6KA6 (GenBank Accession No. NM_014496), HTATSF1 (GenBank Accession No. NM_014500), PHF16 (GenBank Accession No. NM_014500), PHF16 (GenBank Accession No. Accession No. NM_015686), WWC3 (GenBank Accession No. NM_015691), APLN (GenBank Accession No. NM_017413), PLXNA3 (GenBank Accession No. NM_017514), NUDT11 (GenBank Accession No. NM_018159), GABRQ (GenBank Accession No. NM_018558). , SLC10A3 (GenBank Accession No. NM_019848), PCDH19 (GenBank Accession No. NM_020766), WNK3 (GenBank Ac cession No. NM_020922), XK (GenBank Accession No. NM_021083), FAM3A (GenBank Accession No. NM_021806), TMEM47 (GenBank Accession No. NM_031442), CD99L2 (GenBank Accession No. NM_031462), SH3KBP1 (GenBank Accession No. NM_031892), PDZD4 GenBank Accession No. NM_032512), SLC9A7 (GenBank Accession No. NM_032591), DACH2 (GenBank Accession No. NM_053281), SYN1 (GenBank Accession No. NM_133499), DOCK11 (GenBank Accession No. NM_144658), FAM123B (GenBank Accession No. NM_144658), FAM123B (GenBank Accession NM_152424) ), KLHL34 (GenBank Accession No. NM_153270), PTCHD1 (GenBank Accession No. NM_173495), DCAF12L1 (GenBank Accession No. NM_178470), UBE2A (GenBank Accession No. NM_181762), LINC00086 (GenBank Accession No. NR00087) LINC00086 (GenBank Accession No. NR_024343) Accession No. NR_024493), APOO (GenBank Accession No. NR_026545), LOC158572 (GenBank Accession No. NR_026742), LOC100272228 (GenBank Accession No. NR_027456), LOC100303728 (GenBank Accession No. NR_028317), MIR718 (GenBank Accession No. NR_028317443), MIR718. , RAI2 (GenBank Accession No. NR_033348), SCML2 (GenBank Accession No. NR_033 717), LOC100129662 (GenBank Accession No. NR_038405), and LOC100506757 (GenBank Accession No. NR_038998).

More preferably, the gene located on the X chromosome of the present invention consists of SLITRK4 (GenBank Accession No. NM_001184750), EMD (GenBank Accession No. NM_000117), ZIC3 (GenBank Accession No. NM_003413) and CXorf40A (GenBank Accession No. NM_001171908). It may be one or more genes selected from the group.

All of the genes described above are present on the X chromosome, and the level of methylation of their promoters is 4 times higher than that of a normal person in psoriasis patients. This characteristic of the gene promoter is disclosed for the first time in the present invention.

In one embodiment of the present invention, Naive CD4+ cells were isolated from the blood of psoriasis patients and normal people, and then genomic DNA thereof was isolated to measure methylation levels of promoters and gene bodies of all chromosomes. As a result, it was confirmed that in the case of psoriasis patients, the methylation level of the promoter on the X chromosome was specifically higher than that of the normal person. In addition, in the case of atopic patients, which are T cell-related skin diseases such as psoriasis, it was confirmed that the methylation level of the promoter on the X chromosome did not change, and the change was confirmed to be a psoriasis-specific change (see FIG. 2).

In another embodiment of the present invention, the methylation level of a gene-specific promoter on the X chromosome of a normal person and a patient with psoriasis was measured and compared. As a result, it was confirmed that among the 124 genes that showed a change in methylation, the degree of hypermethylation of 121 genes located on the X chromosome was particularly high, and promoter hypermethylation was more than four times higher than that of a normal person (see Table 2).

In another embodiment of the present invention, the level of methylation was measured by separating genes related to the immune system on the chromosome. As a result, it could be confirmed that the genes related to the immune system (marked in red) located in the X chromosome were hypermethylated (see FIG. 3).

As described above, the average methylation level of the promoter of the gene located on the X chromosome of the psoriasis patient is specifically higher than that of the normal control group, and the methylation level of the promoter of some genes is significantly higher in the psoriasis patient, so it can be used as a diagnostic marker for psoriasis. This point is disclosed for the first time in the present invention.

Accordingly, the present invention provides a composition for diagnosing psoriasis comprising an agent measuring the methylation level of a promoter of a gene located on the X chromosome.

The composition of the present invention is characterized in that it comprises an agent for measuring the methylation level of a promoter of a gene located on the X chromosome.

The gene located on the X chromosome is as described above.

The preparation is a method for measuring the methylation level of a known nucleic acid, for example, Solexa sequencing, methylated-CpG island recovery assay (MIRA), PCR, methylation specific PCR (methylation specific) by measuring the methylation level of the promoter of all or individual genes located on the X chromosome. PCR), real time methylation specific PCR, PCR using methylated DNA-specific binding protein, quantitative PCR, pyrosequencing, and bisulfite sequencing. A substance specific to the promoter of the gene located may be a substance specific to the promoter, and the substance specific to the promoter may be a primer specific to the promoter of the gene located on the X chromosome, preferably, a methylation specific PCR (MSP) primer.

The primers specific for the promoter of the gene located on the X chromosome are preferably LOC339822 (GenBank Accession No. NR_033880), FKBP6 (GenBank Accession No. NM_003602), TRIM50 (GenBank Accession No. NM_178125), ABCD1 (GenBank Accession No. NM_000033) ), EMD (GenBank Accession No. NM_000117), HPRT1 (GenBank Accession No. NM_000194), PHKA2 (GenBank Accession No. NM_000292), G6PD (GenBank Accession No. NM_000402), NR0B1 (GenBank Accession No. NM_000475), RPL39 (GenBank Accession No. NM_000475), Accession No. NM_001000), MAP3K15 (GenBank Accession No. NM_001001671), ZDHHC9 (GenBank Accession No. NM_001008222), KIAA2022 (GenBank Accession No. NM_001008537), DNASE1L1 (GenBank Accession No. NMAT1 (GenBank Accession No. , NHSL2 (GenBank Accession No. NM_001013627), DCAF12L2 (GenBank Accession No. NM_001013628), CXorf40B (GenBank Accession No. NM_001013845), VMA21 (GenBank Accession No. NM_001017980), RGAG4 (GenBank Accession NM_001017980), RGAG4 (GenBank Accession No. No. NM_001031855), SCML1 (GenBank Accession No. NM_001037540), PRPS2 (GenBank Accession No. NM_001039091), GPRASP1 (GenBank Accession No. NM_001099411), MAGIX (GenBank Accession No. NM_001099680), ANKRD58 (GenBank Accession No. NM_001105576), MECP2 (GenBank Accession No. NM_001110792), CASK (GenBank Accession No. NM_001110792), CASK (GenBank Accession No. GenBank Accession No. NM_001127197), CLCN5 (GenBank Accession No. NM_001127899), FAM58A (GenBank Accession No. NM_001130997), FAM127B (GenBank Accession No. NM_001134321), PNCK (GenBank Accession No. NM_001135740_001), NM_001135740_001, NBank ), OTUD5 (GenBank Accession No. NM_001136157), BCAP31 (GenBank Accession No. NM_001139441), PDK3 (GenBank Accession No. NM_001142386), DKC1 (GenBank Accession No. NM_001142463), IKBKG (GenBank Accession No. NM_001255), FHL1145255 Accession No. NM_001159703), FAM104B (GenBank Accession No. NM_001166704), MAP7D2 (GenBank Accession No. NM_001168465), CNKSR2 (GenBank Accession No. NM_001168649), AFF2 (GenBank Accession No. NM_001169124), CXorfion. , MBNL3 (GenBank Accession No. NM _001170704), SRPX (GenBank Accession No. NM_001170750), CXorf40A (GenBank Accession No. NM_001171908), TMEM185A (GenBank Accession No. NM_001174092), MAMLD1 (GenBank Accession No. NM_001177465), PPP1R3F (GenBank Accession No.TR. GenBank Accession No. NM_001184898), MSL3 (GenBank Accession No. NM_001193270), RBM10 (GenBank Accession No. NM_001204467), DUSP9 (GenBank Accession No. NM_001395), GPC4 (GenBank Accession No. NM_001448), GDI. ), IL13RA1 (GenBank Accession No. NM_001560), IRAK1 (GenBank Accession No. NM_001569), SHROOM2 (GenBank Accession No. NM_001649), MPP1 (GenBank Accession No. NM_002436), SUV39H1 (GenBank Accession No. NM_003173) Accession No. NM_003413), IRS4 (GenBank Accession No. NM_003604), FGF13 (GenBank Accession No. NM_004114), IDH3G (GenBank Accession No. NM_004135), NDUFA1 (GenBank Accession No. NM_004541), RPS6KA3 (GenBank Accession No. NM_004541), RPS6KA3 (GenBank Accession No. 004586) , RAB33A (GenBank Accession No. NM_004794), HMGB3 (GenBank Accession No. NM_005342), SOX3 (GenBank Accession No. NM_005634), PQBP1 (GenBank Accession No. NM_005710), RPL10 (GenBank Accession No. NM_006013), HDAC6 (GenBank Accession No. NM_006044), PRICKLE3 (GenBank Accession No. NM_006150), SSR4 (SSR4), SSR_006 GenBank Accession No. NM_006280), SLC16A2 (GenBank Accession No. NM_006517), TFE3 (GenBank Accession No. NM_006521), RBM3 (GenBank Accession No. NM_006743), RNF113A (GenBank Accession No. NM_006978), WDR45 (GenBank Accession No. NM_006978), WDR45 (GenBank Accession No. ), ZNF41 (GenBank Accession No. NM_007130), FTSJ1 (GenBank Accession No. NM_012280), PNMA3 (GenBank Accession No. NM_013364), UBL4A (GenBank Accession No. NM_014235), RPS6KA6 (GenBank Accession No. NM_014496) Accession No. NM_014500), PHF16 (GenBank Accession No. NM_014735), FAM155B (GenBank Accession No. NM_015686), WWC3 (GenBank Accession No. NM_015691), APLN (GenBank Accession No. NM_017413), PLXNA3 (GenBank Accession No. , NUDT11 (GenBank Accession No. NM_018159), GABRQ (GenBank Accession No. NM_018558), SLC10A3 (GenBank Acc ession No. NM_019848), PCDH19 (GenBank Accession No. NM_020766), WNK3 (GenBank Accession No. NM_020922), XK (GenBank Accession No. NM_021083), FAM3A (GenBank Accession No. NM_021806), TMEM47 (GenBank Accession No. NM_031442), CD99L_031442 GenBank Accession No. NM_031462), SH3KBP1 (GenBank Accession No. NM_031892), PDZD4 (GenBank Accession No. NM_032512), SLC9A7 (GenBank Accession No. NM_032591), DACH2 (GenBank Accession No. NM_13349981), SYN1 (GenBank Accession No. NM_053281). ), DOCK11 (GenBank Accession No. NM_144658), FAM123B (GenBank Accession No. NM_152424), KLHL34 (GenBank Accession No. NM_153270), PTCHD1 (GenBank Accession No. NM_173495), DCAF12L1 (GenBank Accession No. NM_178470), UBEank Accession No. NM_181762), LINC00086 (GenBank Accession No. NR_024359), LINC00087 (GenBank Accession No. NR_024493), APOO (GenBank Accession No. NR_026545), LOC158572 (GenBank Accession No. NR_026742), LOC100272228 (GenBank Accession No. NR_026742), LOC100272228 (GenBank Accession No. NR_026742) , LOC100303728 (GenBank Accession No. NR_028443), MIR718 (GenBank Accession No. NR_03 1757), RAI2 (GenBank Accession No. NR_033348), SCML2 (GenBank Accession No. NR_033717), LOC100129662 (GenBank Accession No. NR_038405), and LOC100506757 (GenBank Accession No. NR_038998) may be specific primers for the promoter of one or more genes selected from the group consisting of, and preferably May be a primer selected from the group consisting of SEQ ID NOs: 1 to 8, more preferably primers for SLITRK4 are primer pairs represented by SEQ ID NOs: 1 and 2, and primers for EMD are primers represented by SEQ ID NOs: 3 and 4 Pairs, primers for ZIC3 may be primer pairs represented by SEQ ID NOs: 5 and 6, and primers for CXorf40A may be primer pairs represented by SEQ ID NOs: 7 and 8.

The primers are single-stranded under suitable conditions in an appropriate buffer (e.g., 4 different nucleotide triphosphates and a polymerizing agent such as DNA, RNA polymerase or reverse transcriptase) and a suitable temperature to serve as a starting point for template-directed DNA synthesis. Refers to an oligonucleotide. The appropriate length of the primer may vary depending on the intended use, but is usually 15 to 30 nucleotides. Short primer molecules generally require a lower temperature to form a stable hybrid with the template. The primer sequence need not be completely complementary to the template, but must be sufficiently complementary to hybridize to the template.

In one embodiment of the present invention, the methylation of a normal person and a psoriasis patient was compared using a primer pair of genes showing a specific methylation tendency in psoriasis patients. As a result of measuring the methylation level of the promoter of the gene located on the X chromosome using the primers of the present invention, it was confirmed that the methylation level of the psoriasis patient group was significantly higher than that of the normal person (see FIG. 4).

In order to achieve another object of the present invention, the present invention provides a kit for diagnosing psoriasis comprising an agent for measuring the methylation level of a promoter of a gene located on the X chromosome.

Genetic diagnosis of psoriatic disease is possible by using the diagnostic kit of the present invention. The kit of the present invention includes an agent for measuring the methylation level of a promoter of a gene located on the X chromosome (for example, a primer pair capable of measuring the methylation level of a promoter of a gene located on the X chromosome), and analysis of the methylation level of nucleic acids Tools or reagents known in the art used for, for example, dNTP, polymerases of various kinds, and coloring agents may be further included.

As described above, the present invention provides a method for detecting methylation of a promoter of a gene located on the X chromosome to provide information necessary for the diagnosis of psoriasis, and a composition for diagnosis of psoriasis comprising an agent capable of measuring the methylation level. The method and composition of the present invention is effective in diagnosing psoriasis because it can provide genetic information in the diagnosis of psoriatic skin disease.

1 is a graph comparing the Genome-wide dMES values of psoriasis and atopic patients analyzed in units of 10 kb (dMES of Psoriasis: dMES values between psoriasis patients and normal subjects, dMES of AD: dMES values between atopic patients and normal subjects).
2 is a graph showing a result of comparing the dMES values of each promoter and genebody by chromosome by comparing naive CD4+ T cells of psoriasis and atopic patients with normal groups (P: promoter, G: Gene body ), Psoriasis: psoriasis patient, AD: atopic patient).
3 is a graph showing the results of comparing the dMES values of each promoter and genebody with an immune response-related gene (red) for each chromosome by comparing naive CD4+ T cells of psoriasis and atopic patients with a normal group (P: Promoter ), G: Gene body, Psoriasis: psoriasis patient, AD: atopy patient).
Figure 4 is a photograph and graph of experimental results comparing the methylation levels of SLITRK4, EMD, ZIC3, and CXorf40A genes in psoriasis patients and normal people (Normal: normal people, Psoriasis: psoriasis patients, Density (fold): normal people's methylation level 1 The number of times indicated by

Hereinafter, the present invention will be described in detail.

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

< Example 1>

Peripheral blood Naive CD4 ⁺ T cell DNA secure

<1-1> Selection of research subjects

Catholic medical school from 12 and 15 male patients with plaque type psoriasis and atopy, respectively, and 10 male patients in the normal control group, among adults 15 years of age or older who have a family history according to the clinician's criteria and have not received treatment for the past two years. With the approval of the Bioethics Review Committee, volunteer participants who fully understood and agreed to the explanatory text for the study were selected.

<1-2> Naive CD4 ⁺ Isolation of T cells

After collecting about 60-120 ml of peripheral blood from the study subjects, it was diluted one-fold with physiological saline containing 2 mM EDTA and phosphate buffer solution, and then peripheral blood mononuclear cells (PBMC; Peripheral Blood Mononuclear Cell) was isolated.

Using Naive CD4 ⁺ T cell isolation kit II (Order no.130-094-131, MACScell separation reagent, Miltenyi Biotec Inc, Germany), separate biotin-conjugated antibody cocktail and biotin micro-bead according to the manual of the kit. The resulting PMBC was treated ^{to isolate Naive CD4 +} T cells.

To verify that the separated cells are Naive CD4 ⁺ T cells, the separated cells were centrifuged at 4°C for 5 minutes at 1000 rpm, and then the cells were diluted with 1 ml of a phosphate buffer solution (PBS). -20℃ 4ml of ethanol was added and fixed at 4℃ for 1 hour. After centrifuging the immobilized cells, it was diluted in 1 ml of PBS and 100 ul (1 mg/ml) of antibody (FITC Anti-Human CD45RA (Cat. 555488, BD Biosciences, USA), PE Anti-Human CD4 (Cat. 12-). 0049-71, eBioscience, USA)) was added and reacted at room temperature for 5-10 minutes, and then analyzed with a flow cytometer (FACS Calibur (Beckon Dickinson, USA)). As a result, it was confirmed that more than 90% of the isolated cells were Naive CD4 ^{+ T cells.}

<1-3> Naive CD4 ⁺ T cell genomic DNA Separation

Genomic DNA was obtained from the verified Naive CD4 ⁺ T cells using the DNeasy Blood & Tissue Kit (Cat. 69504, QIAGEN, Germany) of QIAGEN. Experiments were conducted according to the kit's manual (Blood and Body Fluid Spin Protocol). Proteinase K-treated Naive CD4+ T cells were dissolved in a buffer solution, and the sample was placed on a DNA spin column and centrifuged at 8000 rpm. The DNA adsorbed on the column was washed with a washing buffer and then separated using an elution buffer. The amount and purity of the isolated genomic DNA were measured by UV spectrophotometric colorimetric measurement.

As a result of measuring the amount of isolated genomic DNA, it was about 1,800 to 20,000 ng, and the purity of gDNA (260/280) was measured to be about 1.9 to 2.1.

< Example 2>

Naive CD4 ⁺ Of T cells and control DNA methylation compare

<2-1> methylated DNA Selective separation of

For methylated DNA selection, MIRA (Methylated CpG Island Recovery Assay) was used in BMC Med Genomics. 2011 Dec 2;4:82, J Thorac Oncol. 2012 Jan;7(1):20-33. First, the region that does not contain CpG was cut using the restriction enzyme MseI (5'-TTAA), which recognizes and cuts the TTAA sequence of genomic DNA, and the cut DNA fragment was ligation with the linker. After binding the purified methylated DNA fragment with GST-MBD2b and His-MBD3L1 proteins, non-specific binding DNA was removed, and TE buffer (Tris-HCl-) containing RNase A (100 ug, Qiagen) and Proteinase K (15 ug, Qiagen). EDTA buffer) 30ul was used to recover the bound DNA.

<2-2> separated DNA of PCR process

The DNA fragment prepared in the MIRA step was linear amplified by PCR using a linker primer (upper strand sequence, 5-TAGAATTCAGATCTCCCG-3 (SEQ ID NO: 9), lower strand sequence, 3-CTTAAGTCTAGAGGGCCCAGTGGCG-5 (SEQ ID NO: 10)). The amplified DNA was separated by gel electrophoresis, and DNA of about 200-500 bp was identified, and then separated through gel extraction. The isolated DNA was analyzed for genome-wide methylation using llumina GA sequencing (Illumina Inc, USA). Sequence tags were created in the human genome of NCBI Build 36.1 assembly based on the University of California Santa Cruz [UCSC, (http://genome.ucsc.edu)] hg18 database using Solexa Analysis Pipeline (version 0.3.0). Has been mapped. The mapped sequencing results were compatible with the UCSC Genome Browser, and the read sequencing data was transformed into browser extensible data (BED) to compare more specific methylation values. 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).

By tagging one DNA fragment every 200bp, tagging was carried out in areas with a lot of methylation for each gene site. DNA fragments mapped every 1 kb were compared with the total number of DNA fragments in the genome in order to find out the regions with a lot of methylation. As a value for comparing the degree of methylation, the Methylation Enrichment Score (MES) was adjusted by the overall methylation count of the genome size (15005528*200 bp), and genes divided at 200 bp intervals by the promoter size (8*200 bp). The average value of the methylation count was calculated as log2.

The equation to obtain the Methylation Enrichment Score (MES) is as follows.

dMES is the obtained patient's MES value minus the normal person's MES value, and represents the difference between the methylation values of the patient group and the normal group in a specific gene.

<2-3> Methylation comparison result

1) Genome-wide analysis

The differences in methylation were compared using dMES values for psoriasis and atopy. The whole genome was divided by 10 kbp intervals, and then the obtained dMES values were averaged.

As a result, as shown in Fig. 1, specific hypomethylated sites were observed in psoriasis patients. A total of 26 sites showed a specific hypomethylation pattern in psoriasis patients compared to atopy, and most of them were found to be close to centromere. The 26 sites where the methylation change occurred can be confirmed in the following [Table 1]. Among these, it can be seen that the MES of the psoriasis patient on chromosome 19 (chr19) is less than that of the normal control patient by 3.2165. This means that methylation at chr19 occurred more than eight times more than those with psoriasis in the control patients.

Genome-wide analysis of naive CD4+ T cell DNA methylation No Chrom Start End Size Ave. AD MES Ave. Psoriasis MES Ave. Normal MES One chr2 90960000 90979999 20000 5.9467 2.2228 5.0041 2 chr2 91630000 91639999 10000 4.3832 1.3917 3.5042 3 chr4 48800000 48819999 20000 4.7058 1.7658 4.0558 4 chr4 48840000 48849999 10000 5.5567 2.3016 4.8005 5 chr4 49330000 49349999 20000 5.1519 1.9123 4.5212 6 chr7 61384000 61393999 10000 5.9675 1.9597 4.9555 7 chr7 61424000 61433999 10000 6.0016 2.5144 5.0224 8 chr7 61604000 61613999 10000 5.0151 0.8384 3.4686 9 chr10 38810000 38859999 50000 3.7152 0.9621 3.2825 10 chr10 38910000 38929999 20000 4.9415 1.7810 4.4303 11 chr10 39120000 39189999 70000 4.6121 1.0283 3.7234 12 chr10 41680000 41719999 40000 6.4954 3.1986 5.8545 13 chr10 41850000 41859999 10000 3.6162 0.2335 2.2396 14 chr10 42110000 42139999 30000 3.8104 1.0555 3.2415 15 chr16 33780000 33809999 30000 4.6706 1.6417 4.0012 16 chr16 34040000 34049999 10000 5.1588 2.0265 4.4272 17 chr16 44950000 45009999 60000 5.2025 2.1858 4.4902 18 chr19 32421000 32430999 10000 6.3821 1.3305 4.5470 19 chr20 29268000 29297999 30000 4.2271 1.2049 3.6680 20 chr21 9799765 9849764 50000 3.8696 1.2113 3.7030 21 chr21 9859765 9879764 20000 3.6943 0.9371 3.3992 22 chr22 15230000 15239999 10000 5.7739 2.1115 5.0009 23 chrY 11910000 11919999 10000 4.9257 2.0048 4.2963 24 chrY 12110000 12149999 40000 3.7456 0.8108 3.3093 25 chrY 12310000 12379999 70000 4.1894 0.9109 3.4392 26 chrY 57380000 57389999 10000 3.8400 1.6228 3.6754

2) Genetic unit analysis

In order to obtain more specific results, the change in methylation by gene unit was investigated. Psoriasis and atopy, respectively, were examined for changes in the methylation of promoter and gene body by chromosome.

As a result, in the case of Promoter, a prominent hypermethylation pattern could be found in the X chromosome of psoriasis, whereas no significant change was found in atopy (see FIG. 2). In the case of the gene body, neither psoriasis nor atopy could find chromosomes whose methylation patterns were clearly changed. Among the hypermethylated promoters in the promoter part of psoriasis Naive CD4+ T cells, dMES values of 2 or more (more than 4 times the methylation compared to normal) were identified, and as a result, 124 genes were obtained, all of which were CpG islands (CpGI ) Had. In addition, it was confirmed that 121 of the 124 genes were located on the X chromosome. Detailed gene information is shown in Table 2.

In particular, the EMD gene (Ref gene ID: NM_000117) of the X chromosome had a dMES value of 4.92, which means that methylation ^{took place 30.27 times (2 4.92} times) more. Therefore, methylation of the EMD gene can be used as a biomarker for the prevention and detection of psoriasis.

Genes hypermethylated with dMES of 2 or more in the promoter area of Naive CD4+ T cells in psoriasis patients No. Refgene ID Chromosome Symbol dMES CpGi One NR_033880 chr2 LOC339822 2.2934 O 2 NM_003602 chr7 FKBP6 2.1914 O 3 NM_178125 chr7 TRIM50 2.1914 O 4 NM_000033 chrX ABCD1 2.5999 O 5 NM _000117 chrX EMD 4.9200 O 6 NM_000194 chrX HPRT1 2.3173 O 7 NM_000292 chrX PHKA2 2.1953 O 8 NM_000402 chrX G6PD 3.6860 O 9 NM_000475 chrX NR0B1 2.1167 O 10 NM_001000 chrX RPL39 2.6402 O 11 NM_001001671 chrX MAP3K15 2.2070 O 12 NM_001008222 chrX ZDHHC9 2.8597 O 13 NM_001008537 chrX KIAA2022 2.3434 O 14 NM_001009934 chrX DNASE1L1 2.7325 O 15 NM_001011657 chrX ZMAT1 2.1664 O 16 NM_001013627 chrX NHSL2 2.2089 O 17 NM_001013628 chrX DCAF12L2 2.2737 O 18 NM_001013845 chrX CXorf40B 3.1290 O 19 NM_001017980 chrX VMA21 2.5180 O 20 NM_001024455 chrX RGAG4 2.5282 O 21 NM_001031855 chrX LONRF3 2.5864 O 22 NM_001037540 chrX SCML1 2.6793 O 23 NM_001039091 chrX PRPS2 2.2086 O 24 NM_001099411 chrX GPRASP1 2.0209 O 25 NM_001099680 chrX MAGIX 2.2078 O 26 NM_001105576 chrX ANKRD58 2.6353 O 27 NM_001110792 chrX MECP2 2.0885 O 28 NM_001126054 chrX CASK 3.1994 O 29 NM_001127197 chrX ELF4 3.3991 O 30 NM_001127899 chrX CLCN5 2.1093 O 31 NM_001130997 chrX FAM58A 2.6127 O 32 NM_001134321 chrX FAM127B 2.3806 O 33 NM_001135740 chrX PNCK 3.4766 O 34 NM_001135998 chrX NDUFB11 2.1788 O 35 NM_001136157 chrX OTUD5 4.1870 O 36 NM_001139441 chrX BCAP31 3.3070 O 37 NM_001142386 chrX PDK3 2.3675 O 38 NM_001142463 chrX DKC1 2.1097 O 39 NM_001145255 chrX IKBKG 3.6860 O 40 NM_001159703 chrX FHL1 2.5184 O 41 NM_001166704 chrX FAM104B 2.1338 O 42 NM_001168465 chrX MAP7D2 2.4083 O 43 NM_001168649 chrX CNKSR2 3.2990 O 44 NM_001169124 chrX AFF2 2.0781 O 45 NM_001169574 chrX CXorf58 2.2351 O 46 NM_001170704 chrX MBNL3 2.3593 O 47 NM_001170750 chrX SRPX 2.0245 O 48 NM_001171908 chrX CXorf40A 2.7477 O 49 NM_001174092 chrX TMEM185A 2.5820 O 50 NM_001177465 chrX MAMLD1 3.5480 O 51 NM_001184745 chrX PPP1R3F 2.6912 O 52 NM_001184750 chrX SLITRK4 3.3013 O 53 NM_001184898 chrX PHF8 2.2572 O 54 NM_001193270 chrX MSL3 3.5714 O 55 NM_001204467 chrX RBM10 2.5140 O 56 NM_001395 chrX DUSP9 2.4662 O 57 NM_001448 chrX GPC4 4.6545 O 58 NM_001493 chrX GDI1 2.8629 O 59 NM_001560 chrX IL13RA1 2.5696 O 60 NM_001569 chrX IRAK1 2.9617 O 61 NM_001649 chrX SHROOM2 2.2563 O 62 NM_002436 chrX MPP1 2.1068 O 63 NM_003173 chrX SUV39H1 2.8446 O 64 NM_003413 chrX ZIC3 3.5286 O 65 NM_003604 chrX IRS4 2.3491 O 66 NM_004114 chrX FGF13 2.3473 O 67 NM_004135 chrX IDH3G 2.9569 O 68 NM_004541 chrX NDUFA1 3.1296 O 69 NM_004586 chrX RPS6KA3 3.1774 O 70 NM_004794 chrX RAB33A 2.5125 O 71 NM_005342 chrX HMGB3 3.0501 O 72 NM_005634 chrX SOX3 3.4033 O 73 NM_005710 chrX PQBP1 2.4486 O 74 NM_006013 chrX RPL10 3.2834 O 75 NM_006044 chrX HDAC6 3.6500 O 76 NM_006150 chrX PRICKLE3 2.5810 O 77 NM_006280 chrX SSR4 2.4967 O 78 NM_006517 chrX SLC16A2 2.0889 O 79 NM_006521 chrX TFE3 2.3790 O 80 NM_006743 chrX RBM3 2.0082 O 81 NM_006978 chrX RNF113A 2.7921 O 82 NM_007075 chrX WDR45 2.2069 O 83 NM_007130 chrX ZNF41 2.6112 O 84 NM_012280 chrX FTSJ1 2.6089 O 85 NM_013364 chrX PNMA3 2.6468 O 86 NM_014235 chrX UBL4A 2.9055 O 87 NM_014496 chrX RPS6KA6 2.2066 O 88 NM_014500 chrX HTATSF1 2.2364 O 89 NM_014735 chrX PHF16 2.1667 O 90 NM_015686 chrX FAM155B 4.7008 O 91 NM_015691 chrX WWC3 3.1109 O 92 NM_017413 chrX APLN 2.0696 O 93 NM_017514 chrX PLXNA3 2.7487 O 94 NM_018159 chrX NUDT11 2.5352 O 95 NM_018558 chrX GABRQ 2.2694 O 96 NM_019848 chrX SLC10A3 2.2025 O 97 NM_020766 chrX PCDH19 2.8862 O 98 NM_020922 chrX WNK3 2.8100 O 99 NM_021083 chrX XK 2.5765 O 100 NM_021806 chrX FAM3A 2.1459 O 101 NM_031442 chrX TMEM47 2.1632 O 102 NM_031462 chrX CD99L2 2.4714 O 103 NM_031892 chrX SH3KBP1 3.7231 O 104 NM_032512 chrX PDZD4 2.2190 O 105 NM_032591 chrX SLC9A7 2.6570 O 106 NM_053281 chrX DACH2 2.8199 O 107 NM_133499 chrX SYN1 2.5066 O 108 NM_144658 chrX DOCK11 2.1752 O 109 NM_152424 chrX FAM123B 2.5042 O 110 NM_153270 chrX KLHL34 2.3549 O 111 NM_173495 chrX PTCHD1 3.5095 O 112 NM_178470 chrX DCAF12L1 2.3477 O 113 NM_181762 chrX UBE2A 2.0157 O 114 NR_024359 chrX LINC00086 2.3290 O 115 NR_024493 chrX LINC00087 2.3955 O 116 NR_026545 chrX APOO 2.1788 O 117 NR_026742 chrX LOC158572 2.1505 O 118 NR_027456 chrX LOC100272228 3.1290 O 119 NR_028443 chrX LOC100303728 2.4072 O 120 NR_031757 chrX MIR718 2.9617 O 121 NR_033348 chrX RAI2 2.7369 O 122 NR_033717 chrX SCML2 3.0486 O 123 NR_038405 chrX LOC100129662 2.0852 O 124 NR_038998 chrX LOC100506757 2.6667 O

3) Immune-related gene analysis

Using the Gene Ontology server (“immune system” process term (GO:0002376)), 1604 genes related to the immune response were obtained, and dMES were compared with genes excluding 1604 for each chromosome.

As a result of comparison, the immune-related genes on the X chromosome showed a higher methylation level than those that did not have a large difference, and there was no obvious change in the other chromosomes except for the X chromosome (see Table 3).

Among the genes in Table 3, in particular, the OTUD5 gene of the X chromosome (Ref gene ID: NM_001136157) had a dMES value of 4.187, indicating that the psoriasis patients had 18 times more methylation than the normal ones.

DMES values of genes related to immune response in psoriasis Refgene ID Symbol Chromosome dMES NM_199173 BGLAP chr1 -1.4430 NM_148964 CTSE chr1 -0.8864 NM_003327 TNFRSF4 chr1 -0.7779 NM_001079874 VAV3 chr1 -0.6674 NM_007053 CD160 chr1 -0.6462 NM_000450 SELE chr1 -0.6035 NM_001206696 IRF6 chr1 -0.5606 NM_172071 RC3H1 chr1 -0.5553 NM_001114101 C1QC chr1 -0.5517 NM_001658 ARF1 chr1 -0.5507 NM_017459 MFAP2 chr1 -0.5422 NM_000952 PTAFR chr1 -0.5197 NM_003051 SLC16A1 chr1 -0.5171 NM_002810 PSMD4 chr1 -0.4069 NM_002953 RPS6KA1 chr1 -0.3918 NM_030787 CFHR5 chr1 -0.3837 NM_004106 FCER1G chr1 -0.3810 NM_000565 IL6R chr1 -0.3724 NM_005621 S100A12 chr1 -0.3597 NM_000715 C4BPA chr1 -0.3568 NM_003820 TNFRSF14 chr1 -0.3464 NM_000983 RPL22 chr1 -0.3399 NM_012486 PSEN2 chr1 -0.3111 NM_020672 S100A14 chr1 -0.3046 NM_001204414 TINAGL1 chr1 -0.2960 NM_201653 CHIA chr1 -0.2939 NM_003189 TAL1 chr1 -0.2931 NM_173065 IL28RA chr1 -0.2807 NM_006027 EXO1 chr1 -0.2668 NM_172313 CSF3R chr1 -0.2609 NM_004833 AIM2 chr1 -0.2577 NM_002922 RGS1 chr1 -0.2470 NM_000491 C1QB chr1 -0.2461 NM_002227 JAK1 chr1 -0.2360 NM_032960 MAPKAPK2 chr1 -0.2332 NM_003921 BCL10 chr1 -0.2318 NM_005026 PIK3CD chr1 -0.2273 NM_001173128 YTHDF2 chr1 -0.2256 NM_001199739 CTSS chr1 -0.2100 NM_002965 S100A9 chr1 -0.1919 NM_020248 CTNNBIP1 chr1 -0.1710 NM_005216 DDOST chr1 -0.1492 NM_005356 LCK chr1 -0.1480 NM_003268 TLR5 chr1 -0.1480 NM_000911 OPRD1 chr1 -0.1402 NM_001190794 NCF2 chr1 -0.1389 NM_001841 CNR2 chr1 -0.1389 NM_002038 IFI6 chr1 -0.1389 NM_001127592 FCGR3A chr1 -0.1389 NM_002113 CFHR1 chr1 -0.1188 NM_005101 ISG15 chr1 -0.1039 NM_020393 PGLYRP4 chr1 -0.1006 NM_144701 IL23R chr1 -0.0929 NM_025073 SIKE1 chr1 -0.0929 NM_001643 APOA2 chr1 -0.0929 NM_001079821 NLRP3 chr1 -0.0929 NM_003465 CHIT1 chr1 -0.0880 NM_001127710 PRG4 chr1 -0.0855 NM_152696 HIPK1 chr1 -0.0855 NM_006135 CAPZA1 chr1 -0.0855 NM_018212 ENAH chr1 -0.0855 NM_002228 JUN chr1 -0.0855 NM_001127215 GFI1 chr1 -0.0855 NM_022768 RBM15 chr1 -0.0855 NM_024626 VTCN1 chr1 -0.0765 NM_006610 MASP2 chr1 -0.0748 NM_001791 CDC42 chr1 -0.0722 NM_001134486 GBP5 chr1 -0.0691 NM_004958 MTOR chr1 -0.0596 NM_173452 FCN3 chr1 -0.0582 NM_003037 SLAMF1 chr1 -0.0563 NM_000066 C8B chr1 -0.0563 NM_006820 IFI44L chr1 -0.0563 NM_001668 ARNT chr1 -0.0563 NM_053282 SH2D1B chr1 -0.0563 NM_000639 FASLG chr1 -0.0563 NM_007207 DUSP10 chr1 -0.0563 NM_005979 S100A13 chr1 -0.0487 NM_002744 PRKCZ chr1 -0.0475 NR_026665 CD58 chr1 -0.0413 NM_001766 CD1D chr1 -0.0413 NM_000567 CRP chr1 -0.0198 NM_004431 EPHA2 chr1 0.0320 NM_002796 PSMB4 chr1 0.0350 NM_183001 SHC1 chr1 0.0417 NM_024575 TNFAIP8L2 chr1 0.0442 NM_005248 FGR chr1 0.0742 NM_001956 EDN2 chr1 0.0820 NM_198053 CD247 chr1 0.1371 NM_016946 F11R chr1 0.1371 NM_002221 ITPKB chr1 0.1371 NM_004481 GALNT2 chr1 0.1371 NM_000748 CHRNB2 chr1 0.1371 NM_003005 SELP chr1 0.1371 NM_021133 RNASEL chr1 0.1371 NM_014053 FLVCR1 chr1 0.1371 NM_021186 ZP4 chr1 0.1425 NM_199454 PRDM16 chr1 0.1426 NM_052891 PGLYRP3 chr1 0.1659 NM_006769 LMO4 chr1 0.2057 NM_000572 IL10 chr1 0.2057 NM_021958 HLX chr1 0.2621 NM_001126 ADSS chr1 0.2621 NM_001166664 CD244 chr1 0.2741 NM_172212 CSF1 chr1 0.3352 NM_000651 CR1 chr1 0.3504 NM_006468 POLR3C chr1 0.3871 NM_002524 NRAS chr1 0.4273 NM_001877 CR2 chr1 0.4273 NM_001677 ATP1B1 chr1 0.4383 NM_015991 C1QA chr1 0.5333 NR_036634 TGFBR3 chr1 0.5376 NM_033131 WNT3A chr1 0.6364 NM_001010926 HES5 chr1 0.6491 NM_030761 WNT4 chr1 0.6799 NM_198551 MIA3 chr1 0.7048 NM_175710 CR1L chr1 0.8175 NM_024494 WNT2B chr1 0.9265 NM_005270 GLI2 chr2 -1.1434 NM_005541 INPP5D chr2 -0.8665 NM_000578 SLC11A1 chr2 -0.7314 NM_003854 IL1RL2 chr2 -0.7311 NM_014440 IL36A chr2 -0.6905 NM_005018 PDCD1 chr2 -0.6649 NM_000251 MSH2 chr2 -0.5966 NM_001079818 ITGA6 chr2 -0.5212 NM_057179 TWIST2 chr2 -0.5164 NR_034059 PSMD1 chr2 -0.4919 NM_002191 INHA chr2 -0.4789 NM_000877 IL1R1 chr2 -0.4788 NM_021209 NLRC4 chr2 -0.4251 NM_005805 PSMD14 chr2 -0.4119 NM_173178 IL36B chr2 -0.3506 NM_003581 NCK2 chr2 -0.3263 NM_032494 ZC3H8 chr2 -0.3082 NM_000634 CXCR1 chr2 -0.2960 NM_173343 IL1R2 chr2 -0.2955 NM_000384 APOB chr2 -0.2951 NM_000577 IL1RN chr2 -0.2939 NM_001130046 CCL20 chr2 -0.2742 NM_199440 HSPD1 chr2 -0.2700 NM_003352 SUMO1 chr2 -0.2456 NM_024782 NHEJ1 chr2 -0.2376 NM_014011 SOCS5 chr2 -0.2300 NM_002664 PLEK chr2 -0.2117 NM_006343 MERTK chr2 -0.1995 NM_001430 EPAS1 chr2 -0.1926 NM_012293 PXDN chr2 -0.1893 NM_004116 FKBP1B chr2 -0.1857 NM_004490 GRB14 chr2 -0.1784 NM_001135592 RPS27A chr2 -0.1751 NM_172102 CD8B chr2 -0.1554 NM_000597 IGFBP2 chr2 -0.1527 NM_022168 IFIH1 chr2 -0.1480 NM_003468 FZD5 chr2 -0.1480 NM_001145000 ITGAV chr2 -0.1418 NM_020458 TTC7A chr2 -0.1268 NM_005683 GPR55 chr2 -0.1237 NM_000090 COL3A1 chr2 -0.1188 NM_000547 TPO chr2 -0.1188 NM_000575 IL1A chr2 -0.0929 NM_006770 MARCO chr2 -0.0929 NM_005400 PRKCE chr2 -0.0855 NM_138559 BCL11A chr2 -0.0855 NM_003856 IL1RL1 chr2 -0.0855 NM_001204110 BCL2L11 chr2 -0.0855 NM_001880 ATF2 chr2 -0.0855 NM_000312 PROC chr2 -0.0793 NM_020651 PELI1 chr2 -0.0563 NM_173202 IL37 chr2 -0.0563 NM_012092 ICOS chr2 -0.0563 NM_017488 ADD2 chr2 -0.0047 NM_000179 MSH6 chr2 0.0043 NM_005633 SOS1 chr2 0.0056 NM_001058 TACR1 chr2 0.0442 NM_212478 FN1 chr2 0.0698 NM_001039569 AP1S3 chr2 0.0780 NM_001616 ACVR2A chr2 0.0807 NM_003507 FZD7 chr2 0.1031 NM_000885 ITGA4 chr2 0.1141 NM_014614 PSME4 chr2 0.1371 NM_003113 SP100 chr2 0.1371 NM_001935 DPP4 chr2 0.1371 NM_002181 IHH chr2 0.1382 NM_003108 SOX11 chr2 0.2113 NM_003183 ADAM17 chr2 0.2741 NM_033358 CASP8 chr2 0.2741 NM_001139517 PRKRA chr2 0.3034 NM_021141 XRCC5 chr2 0.3638 NM_006037 HDAC4 chr2 0.3871 NM_001230 CASP10 chr2 0.3991 NM_134442 CREB1 chr2 0.4312 NM_207519 ZAP70 chr2 0.4366 NM_002166 ID2 chr2 0.8042 NM_014585 SLC40A1 chr2 0.8231 NM_015717 CD207 chr2 0.9215 NM_006722 MITF chr3 -0.7337 NM_130446 KLHL6 chr3 -0.6959 NM_000882 IL12A chr3 -0.6461 NM_139125 MASP1 chr3 -0.6051 NM_001146103 PARP9 chr3 -0.5212 NM_002577 PAK2 chr3 -0.5060 NM_015175 NBEAL2 chr3 -0.4641 NM_032682 FOXP1 chr3 -0.4425 NM_173216 ST6GAL1 chr3 -0.4020 NM_002343 LTF chr3 -0.3766 NM_032638 GATA2 chr3 -0.3695 NM_002215 ITIH1 chr3 -0.3671 NM_144717 IL20RB chr3 -0.3439 NM_017719 SNRK chr3 -0.3064 NM_021105 PLSCR1 chr3 -0.2719 NM_001337 CX3CR1 chr3 -0.2548 NM_002808 PSMD2 chr3 -0.2288 NM_173799 TIGIT chr3 -0.2256 NM_017875 SLC25A38 chr3 -0.2168 NM_004624 VIPR1 chr3 -0.2043 NM_006321 ARIH2 chr3 -0.1952 NM_170780 CD200R1 chr3 -0.1845 NM_001164680 CCR3 chr3 -0.1693 NM_002213 ITGB5 chr3 -0.1663 NM_006219 PIK3CB chr3 -0.1554 NM_006153 NCK1 chr3 -0.1480 NM_001295 CCR1 chr3 -0.1389 NM_001570 IRAK2 chr3 -0.1297 NM_000313 PROS1 chr3 -0.1188 NM_005191 CD80 chr3 -0.1126 NM_031200 CCR9 chr3 -0.0929 NM_003392 WNT5A chr3 -0.0855 NM_001130993 RBP1 chr3 -0.0855 NM_004068 AP2M1 chr3 -0.0746 NM_015720 PODXL2 chr3 -0.0625 NM_001296 CCBP2 chr3 -0.0563 NM_181780 BTLA chr3 -0.0563 NM_000460 THPO chr3 -0.0508 NM_004635 MAPKAPK3 chr3 -0.0339 NM_014814 PSMD6 chr3 -0.0339 NM_001130156 MLF1 chr3 -0.0058 NM_001130845 BCL6 chr3 0.0182 NM_013336 SEC61A1 chr3 0.0516 NM_198793 CD47 chr3 0.1235 NM_005442 EOMES chr3 0.1371 NM_005524 HES1 chr3 0.1371 NM_001190317 IP6K2 chr3 0.1886 NM_138712 PPARG chr3 0.2281 NM_006218 PIK3CA chr3 0.2621 NM_001167618 MLH1 chr3 0.2621 NM_002468 MYD88 chr3 0.2621 NM_002447 MST1R chr3 0.2735 NM_005414 SKIL chr3 0.2741 NM_001947 DUSP7 chr3 0.2741 NM_170662 CBLB chr3 0.3360 NM_001195470 SATB1 chr3 0.3871 NM_004797 ADIPOQ chr3 0.3932 NM_006254 PRKCD chr3 0.5286 NM_005944 CD200 chr3 0.6564 NM_001195106 TLR10 chr4 -0.5695 NM_002620 PF4V1 chr4 -0.5507 NM_052964 CLNK chr4 -0.4036 NM_014331 SLC7A11 chr4 -0.3800 NM_003013 SFRP2 chr4 -0.3447 NM_033437 PDE5A chr4 -0.3325 NM_021973 HAND2 chr4 -0.2836 NM_002994 CXCL5 chr4 -0.2606 NM_001093772 KIT chr4 -0.2415 NM_002753 MAPK10 chr4 -0.2199 NM_001511 CXCL1 chr4 -0.2117 NM_016269 LEF1 chr4 -0.2105 NM_144646 IGJ chr4 -0.1845 NM_005139 ANXA3 chr4 -0.1751 NM_005409 CXCL11 chr4 -0.1751 NM_004310 RHOH chr4 -0.1492 NM_004757 AIMP1 chr4 -0.0929 NM_176801 ADD1 chr4 -0.0855 NM_002253 KDR chr4 -0.0672 NM_001166373 MARCH1 chr4 0.0442 NM_006323 SEC24B chr4 0.0516 NM_004334 BST1 chr4 0.0544 NM_001189 NKX3-2 chr4 0.0607 NM_017628 TET2 chr4 0.0807 NM_004787 SLIT2 chr4 0.0991 NM_002619 PF4 chr4 0.1146 NM_001130691 PPP3CA chr4 0.1371 NM_002090 CXCL3 chr4 0.1371 NM_032991 CASP3 chr4 0.1371 NM_016323 HERC5 chr4 0.1644 NM_005429 VEGFC chr4 0.2065 NM_001957 EDNRA chr4 0.2260 NM_003264 TLR2 chr4 0.3198 NM_001199021 SPON2 chr4 0.3345 NM_005882 MAEA chr4 0.4075 NM_000588 IL3 chr5 -0.7991 NM_014443 IL17B chr5 -0.7791 NM_006650 CPLX2 chr5 -0.6286 NM_004946 DOCK2 chr5 -0.5461 NM_003248 THBS4 chr5 -0.5030 NM_021649 TICAM2 chr5 -0.4433 NM_005242 F2RL1 chr5 -0.3871 NM_005246 FER chr5 -0.3550 NM_001127511 APC chr5 -0.3293 NM_001025071 RPS14 chr5 -0.3235 NM_002609 PDGFRB chr5 -0.3161 NR_033449 TCF7 chr5 -0.2960 NM_000590 IL9 chr5 -0.2668 NM_001746 CANX chr5 -0.2668 NM_005211 CSF1R chr5 -0.2443 NM_000949 PRLR chr5 -0.2409 NM_006467 POLR3G chr5 -0.2409 NM_006846 SPINK5 chr5 -0.2318 NM_000879 IL5 chr5 -0.2242 NM_016103 SAR1B chr5 -0.2044 NM_002188 IL13 chr5 -0.2014 NM_002439 MSH3 chr5 -0.1981 NM_013409 FST chr5 -0.1845 NM_001465 FYB chr5 -0.1693 NM_148672 CCL28 chr5 -0.1693 NM_002187 IL12B chr5 -0.1693 NM_001737 C9 chr5 -0.1492 NM_001193348 MEF2C chr5 -0.1188 NM_001130105 COL4A3BP chr5 -0.1188 NM_004707 ATG12 chr5 -0.1177 NM_001166176 NKX2-5 chr5 -0.1126 NM_000758 CSF2 chr5 -0.0976 NM_003401 XRCC4 chr5 -0.0855 NM_000958 PTGER4 chr5 -0.0855 NM_175920 LNPEP chr5 -0.0563 NM_139017 IL31RA chr5 -0.0563 NM_005546 ITK chr5 -0.0563 NM_001115131 C6 chr5 -0.0109 NM_021982 SEC24A chr5 -0.0109 NM_171825 CAMK2A chr5 -0.0109 NM_005582 CD180 chr5 -0.0019 NM_005921 MAP3K1 chr5 0.1371 NM_000589 IL4 chr5 0.1371 NM_013237 PRELID1 chr5 0.1506 NM_000505 F12 chr5 0.2422 NM_005565 LCP2 chr5 0.2621 NM_004887 CXCL14 chr5 0.2741 NM_001131055 HRH2 chr5 0.3085 NM_003664 AP3B1 chr5 0.3352 NM_001964 EGR1 chr5 0.4722 NM_001145805 IRGM chr5 0.5642 NM_004291 CARTPT chr5 0.8198 NM_003804 RIPK1 chr6 -0.7607 NM_004367 CCR6 chr6 -0.5323 NM_001206966 AGER chr6 -0.5110 NM_002190 IL17A chr6 -0.4740 NM_001178063 C2 chr6 -0.4438 NM_002119 HLA-DOA chr6 -0.4131 NM_018833 TAP2 chr6 -0.3728 NM_001204384 VEGFA chr6 -0.3464 NM_003131 SRF chr6 -0.3439 NM_001136126 CCND3 chr6 -0.3374 NM_001197240 BTN2A2 chr6 -0.3325 NM_004849 ATG5 chr6 -0.3282 NM_178174 TREML1 chr6 -0.2774 NM_002800 PSMB9 chr6 -0.2730 NM_000593 TAP1 chr6 -0.2730 NM_006586 CNPY3 chr6 -0.2712 NM_000594 TNF chr6 -0.2668 NM_006778 TRIM10 chr6 -0.2640 NM_024518 ULBP3 chr6 -0.2613 NM_001718 BMP6 chr6 -0.2609 NM_021135 RPS6KA2 chr6 -0.2609 NM_001455 FOXO3 chr6 -0.2185 NM_001242590 TREM1 chr6 -0.2179 NM_206811 MOG chr6 -0.2117 NM_078467 CDKN1A chr6 -0.2117 NM_021940 SMAP1 chr6 -0.2043 NM_018064 AKIRIN2 chr6 -0.1893 NM_005931 MICB chr6 -0.1845 NM_003545 HIST1H4E chr6 -0.1832 NM_005516 HLA-E chr6 -0.1813 NM_033554 HLA-DPA1 chr6 -0.1784 NM_181337 KAAG1 chr6 -0.1554 NM_025218 ULBP1 chr6 -0.1554 NR_034069 SRPK1 chr6 -0.1480 NM_004155 SERPINB9 chr6 -0.1480 NM_002127 HLA-G chr6 -0.1389 NR_001434 HLA-H chr6 -0.1389 NM_002122 HLA-DQA1 chr6 -0.1310 NM_018965 TREM2 chr6 -0.1188 NM_001199917 PGM3 chr6 -0.1188 NM_001145467 NCR3 chr6 -0.0929 NM_020056 HLA-DQA2 chr6 -0.0929 NM_004666 VNN1 chr6 -0.0929 NM_015093 TAB2 chr6 -0.0855 NM_002117 HLA-C chr6 -0.0855 NM_001160260 CNR1 chr6 -0.0855 NM_001710 CFB chr6 -0.0753 NM_019111 HLA-DRA chr6 -0.0614 NM_001159740 LTA chr6 -0.0563 NM_003206 TCF21 chr6 -0.0475 NM_014028 OSTM1 chr6 -0.0019 NM_001167827 TFEB chr6 0.0167 NM_018950 HLA-F chr6 0.0182 NM_001198 PRDM1 chr6 0.0182 NM_130900 RAET1L chr6 0.0244 NM_139013 MAPK14 chr6 0.0333 NM_001195286 IRF4 chr6 0.0442 NM_004973 JARID2 chr6 0.0516 NM_003107 SOX4 chr6 0.0516 NM_003188 MAP3K7 chr6 0.0516 NM_001001788 RAET1G chr6 0.0703 NM_007355 HSP90AB1 chr6 0.0775 NM_004557 NOTCH4 chr6 0.1235 NM_002116 HLA-A chr6 0.1371 NM_001168389 CITED2 chr6 0.1371 NM_139165 RAET1E chr6 0.1371 NM_005618 DLL1 chr6 0.1371 NM_025217 ULBP2 chr6 0.2621 NM_178014 TUBB chr6 0.2741 NM_006290 TNFAIP3 chr6 0.2741 NM_006208 ENPP1 chr6 0.4266 NM_001161659 MYB chr6 0.5011 NM_172208 TAPBP chr6 0.6051 NM_001732 BTN1A1 chr6 0.8141 NM_000636 SOD2 chr6 1.0049 NM_170610 HIST1H2BA chr6 1.7021 NM_001165413 SERPINE1 chr7 -0.8081 NM_000089 COL1A2 chr7 -0.7271 NR_038121 ELMO1 chr7 -0.4862 NM_001098630 IRF5 chr7 -0.4131 NM_000799 EPO chr7 -0.3961 NM_002889 RARRES2 chr7 -0.3577 NM_014478 CRCP chr7 -0.3568 NM_152739 HOXA9 chr7 -0.3095 NR_003613 PMS2P1 chr7 -0.3034 NM_002991 CCL24 chr7 -0.2917 NM_001206901 TAX1BP1 chr7 -0.2730 NM_001112706 SCIN chr7 -0.2700 NM_007155 ZP3 chr7 -0.2695 NM_000048 ASL chr7 -0.2660 NM_005824 LRRC17 chr7 -0.2621 NM_020979 SH2B2 chr7 -0.2606 NM_001185 AZGP1 chr7 -0.2560 NM_001283 AP1S1 chr7 -0.2409 NM_032464 LAT2 chr7 -0.1845 NM_001165255 MNX1 chr7 -0.1845 NM_002192 INHBA chr7 -0.1751 NR_002217 PMS2CL chr7 -0.1740 NM_031267 CDK13 chr7 -0.1710 NM_207111 RNF216 chr7 -0.1492 NR_003085 PMS2 chr7 -0.1480 NM_006379 SEMA3C chr7 -0.1006 NM_000600 IL6 chr7 -0.0947 NM_000168 GLI3 chr7 -0.0855 NR_027775 PMS2P5 chr7 -0.0855 NM_006072 CCL26 chr7 -0.0855 NM_001204453 PSMC2 chr7 -0.0855 NM_013252 CLEC5A chr7 -0.0855 NM_021130 PPIA chr7 -0.0706 NM_002787 PSMA2 chr7 -0.0563 NM_030961 TRIM56 chr7 -0.0563 NM_001742 CALCR chr7 -0.0487 NM_003508 FZD9 chr7 -0.0252 NM_016118 NUB1 chr7 0.0198 NR_023383 PMS2P11 chr7 0.0470 NM_001220765 IKZF1 chr7 0.0516 NM_024625 ZC3HAV1 chr7 0.0516 NM_032415 CARD11 chr7 0.0516 NM_006908 RAC1 chr7 0.0516 NM_005397 PODXL chr7 0.1225 NM_001724 BPGM chr7 0.1371 NM_006136 CAPZA2 chr7 0.1860 NM_003182 TAC1 chr7 0.2119 NM_019102 HOXA5 chr7 0.2379 NM_006896 HOXA7 chr7 0.2621 NM_018384 GIMAP5 chr7 0.2621 NM_001142574 IMPDH1 chr7 0.2961 NM_172084 CAMK2B chr7 0.3334 NM_000230 LEP chr7 0.4223 NM_182931 MLL5 chr7 0.4507 NM_014817 TRIL chr7 0.4509 NM_007349 PAXIP1 chr7 0.5056 NM_001113239 HIPK2 chr7 1.0809 NM_005218 DEFB1 chr8 -0.6969 NM_001715 BLK chr8 -0.5146 NM_003695 LY6D chr8 -0.4728 NM_015254 KIF13B chr8 -0.4152 NM_003974 DOK2 chr8 -0.4024 NM_001722 POLR3D chr8 -0.3962 NM_003816 ADAM9 chr8 -0.2960 NM_001925 DEFA4 chr8 -0.2910 NR_033818 IKBKB chr8 -0.2380 NM_017780 CHD7 chr8 -0.2335 NM_000497 CYP11B1 chr8 -0.2132 NM_001111097 LYN chr8 -0.2105 NM_005217 DEFA3 chr8 -0.1919 NM_005079 TPD52 chr8 -0.1832 NM_004084 DEFA1 chr8 -0.1554 NM_004331 BNIP3L chr8 -0.0990 NM_001130863 ENPP2 chr8 -0.0929 NM_177531 PKHD1L1 chr8 -0.0904 NM_006904 PRKDC chr8 -0.0855 NM_004674 ASH2L chr8 -0.0855 NM_001831 CLU chr8 -0.0563 NM_003012 SFRP1 chr8 0.0084 NM_005655 KLF10 chr8 0.1141 NM_001135242 NDRG1 chr8 0.1371 NM_181702 GEM chr8 0.1371 NM_030788 TM7SF4 chr8 0.1692 NM_006756 TCEA1 chr8 0.1922 NM_001147 ANGPT2 chr8 0.1976 NM_173176 PTK2B chr8 0.2057 NM_001172815 SLC30A8 chr8 0.3288 NM_145690 YWHAZ chr8 0.3991 NM_001008539 SLC7A2 chr8 0.4646 NM_000912 OPRK1 chr8 0.5030 NM_018440 PAG1 chr8 0.5946 NM_002485 NBN chr8 0.5972 NM_006281 STK3 chr8 0.6659 NM_000787 DBH chr9 -1.4243 NM_001197098 PRSS3 chr9 -0.8941 NM_052814 CARD9 chr9 -0.7171 NM_004479 FUT7 chr9 -0.6686 NM_000608 ORM2 chr9 -0.5655 NR_024514 ADAMTS13 chr9 -0.5637 NM_004188 GFI1B chr9 -0.5340 NM_021138 TRAF2 chr9 -0.4653 NM_003640 IKBKAP chr9 -0.3510 NM_001633 AMBP chr9 -0.3319 NM_002989 CCL21 chr9 -0.2664 NM_014791 MELK chr9 -0.2602 NM_000607 ORM1 chr9 -0.2482 NM_019594 LRRC8A chr9 -0.2409 NM_000459 TEK chr9 -0.2306 NM_006808 SEC61B chr9 -0.2306 NM_058195 CDKN2A chr9 -0.2273 NM_021002 IFNA6 chr9 -0.2043 NM_004473 FOXE1 chr9 -0.1864 NM_014450 SIT1 chr9 -0.1845 NM_004925 AQP3 chr9 -0.1711 NM_002169 IFNA5 chr9 -0.1480 NM_004235 KLF4 chr9 -0.1418 NM_000606 C8G chr9 -0.1349 NM_000136 FANCC chr9 -0.1251 NM_005384 NFIL3 chr9 -0.0964 NM_020124 IFNK chr9 -0.0929 NM_001199641 IL33 chr9 -0.0855 NM_001497 B4GALT1 chr9 -0.0855 NM_016042 EXOSC3 chr9 -0.0855 NM_001244 TNFSF8 chr9 -0.0855 NM_021268 IFNA17 chr9 -0.0563 NM_004972 JAK2 chr9 -0.0413 NM_001010 RPS6 chr9 -0.0001 NM_000050 ASS1 chr9 0.0150 NM_016734 PAX5 chr9 0.0182 NM_005564 LCN2 chr9 0.0307 NM_001130916 TGFBR1 chr9 0.0516 NM_002799 PSMB7 chr9 0.1346 NM_001004354 NRARP chr9 0.1368 NM_014143 CD274 chr9 0.1371 NM_002176 IFNB1 chr9 0.1371 NM_017617 NOTCH1 chr9 0.2388 NM_002173 IFNA16 chr9 0.2621 NM_015837 FCN2 chr9 0.2834 NM_078487 CDKN2B chr9 0.3307 NM_003028 SHB chr9 0.3867 NM_001142287 SEMA4D chr9 0.4091 NM_002003 FCN1 chr9 0.7705 NM_005047 PSMD5 chr9 0.8186 NM_021570 BARX1 chr9 0.8882 NM_022487 DCLRE1C chr10 -0.6443 NM_001786 CDK1 chr10 -0.5638 NM_020975 RET chr10 -0.4655 NM_005041 PRF1 chr10 -0.3962 NR_033494 IL15RA chr10 -0.3962 NM_001077494 NFKB2 chr10 -0.3888 NM_004273 CHST3 chr10 -0.3290 NM_001164490 ADAM8 chr10 -0.2967 NM_001178134 CXCL12 chr10 -0.2335 NR_028034 FAS chr10 -0.2306 NM_000417 IL2RA chr10 -0.1952 NM_000242 MBL2 chr10 -0.1857 NM_001547 IFIT2 chr10 -0.1784 NM_005204 MAP3K8 chr10 -0.1307 NM_001114094 BLNK chr10 -0.1188 NM_006793 PRDX3 chr10 -0.1188 NM_145285 NKX2-3 chr10 -0.1006 NM_020200 PRTFDC1 chr10 -0.0855 NM_020397 CAMK1D chr10 -0.0848 NM_004406 DMBT1 chr10 -0.0563 NM_013274 POLL chr10 -0.0563 NM_006721 ADK chr10 -0.0475 NM_018063 HELLS chr10 -0.0047 NM_031866 FZD8 chr10 0.0011 NM_002051 GATA3 chr10 0.0516 NM_007055 POLR3A chr10 0.0807 NM_002211 ITGB1 chr10 0.1017 NM_004329 BMPR1A chr10 0.1155 NM_001242413 PRKCQ chr10 0.1371 NM_012238 SIRT1 chr10 0.1371 NM_005521 TLX1 chr10 0.1371 NM_004052 BNIP3 chr10 0.1371 NM_182639 HPS1 chr10 0.1626 NM_001278 CHUK chr10 0.2030 NM_172173 CAMK2G chr10 0.2322 NM_145021 MARCH8 chr10 0.2621 NM_003901 SGPL1 chr10 0.2741 NM_021132 PPP3CB chr10 0.2793 NM_002729 HHEX chr10 0.3111 NM_030751 ZEB1 chr10 0.3309 NM_003893 LDB1 chr10 0.3871 NM_001142628 SEC61A2 chr10 0.5771 NM_006504 PTPRE chr10 0.6805 NM_001144914 FGFR2 chr10 0.7380 NM_005180 BMI1 chr10 0.8377 NM_006744 RBP4 chr10 1.2289 NM_000062 SERPING1 chr11 -1.0302 NM_021805 SIGIRR chr11 -0.8272 NM_000207 INS chr11 -0.7700 NM_006435 IFITM2 chr11 -0.6086 NM_003120 SPI1 chr11 -0.5428 NM_000482 APOA4 chr11 -0.5231 NM_000610 CD44 chr11 -0.5036 NM_001335 CTSW chr11 -0.4818 NM_001098503 PTPRJ chr11 -0.4632 NM_005797 MPZL2 chr11 -0.4418 NM_006006 ZBTB16 chr11 -0.3812 NM_001814 CTSC chr11 -0.3786 NM_006093 PRG3 chr11 -0.3512 NM_001741 CALCA chr11 -0.3081 NM_012296 GAB2 chr11 -0.2881 NM_000039 APOA1 chr11 -0.2534 NM_004031 IRF7 chr11 -0.2495 NM_001128620 PAK1 chr11 -0.2152 NM_021034 IFITM3 chr11 -0.2152 NM_001143820 ETS1 chr11 -0.2117 NM_001242607 NCAM1 chr11 -0.1693 NM_002421 MMP1 chr11 -0.1693 NM_005146 SART1 chr11 -0.1689 NM_032531 KIRREL3 chr11 -0.1499 NM_001130101 NR1H3 chr11 -0.1248 NM_002728 PRG2 chr11 -0.1177 NM_130804 MEN1 chr11 -0.1006 NM_175932 PSMD13 chr11 -0.0855 NM_145803 TRAF6 chr11 -0.0855 NM_004223 UBE2L6 chr11 -0.0855 NM_005699 IL18BP chr11 -0.0855 NM_019009 TOLLIP chr11 -0.0847 NM_148976 PSMA1 chr11 -0.0730 NM_000612 IGF2 chr11 -0.0563 NM_000613 HPX chr11 -0.0563 NM_004778 GPR44 chr11 -0.0563 NM_002335 LRP5 chr11 -0.0553 NM_203286 PVRL1 chr11 -0.0339 NM_003357 SCGB1A1 chr11 -0.0249 NM_004356 CD81 chr11 -0.0147 NM_000372 TYR chr11 0.0182 NM_004451 ESRRA chr11 0.0300 NM_030930 UNC93B1 chr11 0.0972 NM_000506 F2 chr11 0.1228 NM_021950 MS4A1 chr11 0.1371 NM_014207 CD5 chr11 0.1371 NM_015973 GAL chr11 0.1381 NM_003824 FADD chr11 0.1764 NM_006288 THY1 chr11 0.2160 NM_015055 SWAP70 chr11 0.2346 NM_138961 ESAM chr11 0.2621 NM_004579 MAP4K2 chr11 0.3136 NM_001039661 TIRAP chr11 0.3307 NM_032966 CXCR5 chr11 0.3311 NM_015368 PANX1 chr11 0.3352 NM_170722 NLRX1 chr11 0.3710 NM_002032 FTH1 chr11 0.3761 NM_001197104 MLL chr11 0.4142 NM_004314 ART1 chr11 0.4273 NM_005247 FGF3 chr11 0.5537 NM_001142676 CHID1 chr11 0.5757 NM_021975 RELA chr11 0.5757 NM_006235 POU2AF1 chr11 0.5804 NM_003377 VEGFB chr11 0.6459 NM_002804 PSMC3 chr11 0.7846 NM_001130442 HRAS chr11 0.8034 NR_026572 PDE2A chr11 0.8476 NM_012305 AP2A2 chr11 0.9327 NM_001142316 LMO2 chr11 0.9719 NR_033421 SLC11A2 chr12 -0.6458 NM_002286 LAG3 chr12 -0.3827 NM_033360 KRAS chr12 -0.3757 NM_001128912 PCBP2 chr12 -0.3632 NM_016546 C1RL chr12 -0.3309 NR_003039 GLYCAM1 chr12 -0.3235 NM_006121 KRT1 chr12 -0.3202 NM_006187 OAS3 chr12 -0.3029 NM_005810 KLRG1 chr12 -0.2621 NM_080549 PTPN6 chr12 -0.2609 NM_013254 TBK1 chr12 -0.2306 NM_000928 PLA2G1B chr12 -0.2135 NM_007334 KLRD1 chr12 -0.2117 NM_014358 CLEC4E chr12 -0.2117 NM_020297 ABCC9 chr12 -0.2014 NM_001184976 NCKAP1L chr12 -0.1952 NM_002535 OAS2 chr12 -0.1952 NM_001130711 CLEC2A chr12 -0.1919 NM_002583 PAWR chr12 -0.1845 NM_000889 ITGB7 chr12 -0.1784 NM_002834 PTPN11 chr12 -0.1656 NM_000924 PDE1B chr12 -0.1546 NM_003348 UBE2N chr12 -0.1492 NM_080387 CLEC4D chr12 -0.1389 NM_001172633 OLR1 chr12 -0.1389 NM_003362 UNG chr12 -0.1389 NM_198213 OASL chr12 -0.1389 NM_020661 AICDA chr12 -0.1188 NM_001142345 CMKLR1 chr12 -0.1188 NM_134324 TARBP2 chr12 -0.1188 NM_000785 CYP27B1 chr12 -0.1188 NM_005419 STAT2 chr12 -0.1126 NM_002205 ITGA5 chr12 -0.0929 NM_004054 C3AR1 chr12 -0.0855 NM_002534 OAS1 chr12 -0.0855 NM_022916 VPS33A chr12 -0.0855 NM_000899 KITLG chr12 -0.0563 NM_000618 IGF1 chr12 -0.0563 NM_194450 CLEC4A chr12 -0.0563 NM_022570 CLEC7A chr12 -0.0563 NM_022652 DUSP6 chr12 -0.0563 NM_021009 UBC chr12 -0.0563 NM_001142523 IRAK3 chr12 -0.0264 NM_001172440 ENDOU chr12 0.0032 NM_003394 WNT10B chr12 0.0516 NM_001143906 TRAFD1 chr12 0.0516 NM_130441 CLEC4C chr12 0.1172 NM_177551 HCAR2 chr12 0.1296 NM_001114182 IRAK4 chr12 0.1371 NM_005475 SH2B3 chr12 0.1371 NM_001242 CD27 chr12 0.1371 NM_018009 TAPBPL chr12 0.1371 NM_003153 STAT6 chr12 0.1371 NM_001733 C1R chr12 0.1494 NM_138473 SP1 chr12 0.2722 NM_020328 ACVR1B chr12 0.3352 NM_004416 DTX1 chr12 0.3671 NR_033948 P2RX7 chr12 0.3871 NM_005430 WNT1 chr12 0.5241 NM_012463 ATP6V0A2 chr12 0.5388 NM_005171 ATF1 chr12 0.6399 NM_000131 F7 chr13 -0.9970 NM_000059 BRCA2 chr13 -0.4503 NM_004119 FLT3 chr13 -0.2470 NM_206937 LIG4 chr13 -0.2168 NM_001160031 FLT1 chr13 -0.1330 NM_020377 CYSLTR2 chr13 -0.0929 NM_000321 RB1 chr13 -0.0563 NM_018386 PCID2 chr13 0.0516 NM_003291 TPP2 chr13 0.1371 NM_002128 HMGB1 chr13 0.1426 NM_001201397 EDNRB chr13 0.4192 NM_001143946 GAS6 chr13 0.4641 NM_003701 TNFSF11 chr13 0.4715 NM_003749 IRS2 chr13 0.6610 NM_032572 RNASE7 chr14 -0.9412 NM_001099780 PSMB11 chr14 -0.5435 NM_001130080 IFI27 chr14 -0.4803 NM_152328 ADSSL1 chr14 -0.4793 NM_012244 SLC7A8 chr14 -0.4740 NM_000270 PNP chr14 -0.4587 NM_005163 AKT1 chr14 -0.3700 NM_006255 PRKCH chr14 -0.3539 NM_182908 DHRS2 chr14 -0.3342 NM_001312 CRIP2 chr14 -0.2960 NM_001126106 SLC7A7 chr14 -0.2742 NM_017999 RNF31 chr14 -0.2700 NM_006084 IRF9 chr14 -0.2621 NM_007318 PSEN1 chr14 -0.2563 NM_002306 LGALS3 chr14 -0.2470 NM_003239 TGFB3 chr14 -0.2274 NM_002802 PSMC1 chr14 -0.2251 NM_000710 BDKRB1 chr14 -0.1857 NM_002818 PSME2 chr14 -0.1845 NM_030755 TMX1 chr14 -0.1813 NM_002806 PSMC6 chr14 -0.1389 NM_021709 SIVA1 chr14 -0.1338 NM_001530 HIF1A chr14 -0.1188 NM_000161 GCH1 chr14 -0.0672 NM_005982 SIX1 chr14 -0.0413 NM_006029 PNMA1 chr14 -0.0339 NM_002791 PSMA6 chr14 0.0442 NM_172314 IL25 chr14 0.1371 NM_016417 GLRX5 chr14 0.1371 NM_145159 JAG2 chr14 0.1502 NM_176783 PSME1 chr14 0.1600 NM_015156 RCOR1 chr14 0.3056 NM_001805 CEBPE chr14 0.3340 NM_002742 PRKD1 chr14 0.3698 NM_017420 SIX4 chr14 0.3991 NM_145726 TRAF3 chr14 1.2942 NM_020980 AQP9 chr15 -0.6229 NM_134261 RORA chr15 -0.4296 NM_018445 SELS chr15 -0.3654 NM_033250 PML chr15 -0.3418 NM_000119 EPB42 chr15 -0.3247 NM_001102667 PSMA4 chr15 -0.2789 NM_000103 CYP19A1 chr15 -0.2683 NM_004498 ONECUT1 chr15 -0.2335 NM_001143785 FES chr15 -0.2135 NM_000057 BLM chr15 -0.2105 NM_004390 CTSH chr15 -0.1865 NM_016166 PIAS1 chr15 -0.1813 NM_017743 DPP8 chr15 -0.1751 NM_003978 PSTPIP1 chr15 -0.1418 NM_207040 TCF12 chr15 -0.1389 NM_001127190 CSK chr15 -0.0964 NM_001130928 MEF2A chr15 -0.0929 NM_004998 MYO1E chr15 -0.0855 NM_004048 B2M chr15 -0.0855 NM_012388 PLDN chr15 -0.0855 NM_016630 SPG21 chr15 -0.0549 NM_001172128 IL16 chr15 -0.0488 NM_006293 TYRO3 chr15 -0.0475 NM_001146030 SEMA7A chr15 -0.0140 NM_002755 MAP2K1 chr15 -0.0004 NM_001110 ADAM10 chr15 0.0138 NM_025240 CD276 chr15 0.0314 NM_183234 RAB27A chr15 0.0807 NM_002201 ISG20 chr15 0.1017 NM_001145104 SMAD3 chr15 0.1330 NM_001191322 GREM1 chr15 0.1371 NM_015995 KLF13 chr15 0.1371 NM_000875 IGF1R chr15 0.1763 NM_005313 PDIA3 chr15 0.1801 NM_003246 THBS1 chr15 0.2741 NR_027654 SMAD6 chr15 0.3257 NM_022162 NOD2 chr16 -0.7500 NM_013278 IL17C chr16 -0.7183 NM_005187 CBFA2T3 chr16 -0.6844 NM_016633 AHSP chr16 -0.6814 NM_004221 IL32 chr16 -0.6552 NM_002987 CCL17 chr16 -0.6112 NM_001198536 MEFV chr16 -0.5363 NM_152456 IL34 chr16 -0.4732 NM_003745 SOCS1 chr16 -0.3161 NM_005950 MT1G chr16 -0.3106 NM_002990 CCL22 chr16 -0.3046 NM_001166395 CHST4 chr16 -0.2376 NM_014387 LAT chr16 -0.2172 NM_000887 ITGAX chr16 -0.2117 NM_000246 CIITA chr16 -0.2043 NM_000101 CYBA chr16 -0.2032 NM_001128 AP1G1 chr16 -0.1710 NM_013292 MYLPF chr16 -0.1650 NM_005849 IGSF6 chr16 -0.1554 NM_005953 MT2A chr16 -0.1492 NM_002661 PLCG2 chr16 -0.1480 NM_001042412 CYLD chr16 -0.1480 NM_001109891 MAPK3 chr16 -0.1126 NM_002996 CX3CL1 chr16 -0.1009 NM_007074 CORO1A chr16 -0.0964 NM_005353 ITGAD chr16 -0.0929 NM_020313 CIAPIN1 chr16 -0.0855 NM_001076785 SLC7A6 chr16 -0.0855 NM_001199174 MLST8 chr16 -0.0779 NM_013258 PYCARD chr16 -0.0563 NM_000418 IL4R chr16 -0.0413 NM_004360 CDH1 chr16 -0.0274 NM_002738 PRKCB chr16 -0.0109 NM_014567 BCAR1 chr16 -0.0082 NM_016326 CKLF chr16 -0.0019 NM_002163 IRF8 chr16 0.0957 NM_005332 HBZ chr16 0.1322 NM_001770 CD19 chr16 0.1341 NM_145659 IL27 chr16 0.1354 NM_016310 POLR3K chr16 0.1371 NM_018119 POLR3E chr16 0.1371 NM_001079846 CREBBP chr16 0.1393 NM_032206 NLRC5 chr16 0.2563 NM_024589 ROGDI chr16 0.3136 NM_005147 DNAJA3 chr16 0.3307 NM_003486 SLC7A5 chr16 0.5346 NM_153813 ZFPM1 chr16 0.5915 NM_031268 PDPK1 chr16 0.5977 NM_058219 EXOSC6 chr16 1.1318 NM_152901 PYDC1 chr16 1.1334 NM_080706 TRPV1 chr17 -1.3886 NM_000759 CSF3 chr17 -1.1073 NM_006344 CLEC10A chr17 -0.9756 NM_005310 GRB7 chr17 -0.8878 NM_012452 TNFRSF13B chr17 -0.8601 NM_024844 NUP85 chr17 -0.8503 NM_152830 ACE chr17 -0.6639 NM_000676 ADORA2B chr17 -0.6014 NM_014922 NLRP1 chr17 -0.4916 NM_013351 TBX21 chr17 -0.4393 NM_002985 CCL5 chr17 -0.4320 NM_002146 HOXB3 chr17 -0.3774 NM_004448 ERBB2 chr17 -0.3597 NM_022059 CXCL16 chr17 -0.3534 NM_000442 PECAM1 chr17 -0.3521 NM_032965 CCL15 chr17 -0.3367 NM_001042492 NF1 chr17 -0.3337 NM_001092 ABR chr17 -0.3208 NM_002805 PSMC5 chr17 -0.3168 NM_005831 CALCOCO2 chr17 -0.3141 NM_003004 SECTM1 chr17 -0.3086 NM_004590 CCL16 chr17 -0.3008 NM_002815 PSMD11 chr17 -0.2990 NM_001081461 JMJD6 chr17 -0.2945 NM_005082 TRIM25 chr17 -0.2931 NM_000625 NOS2 chr17 -0.2376 NM_005533 IFI35 chr17 -0.2300 NM_000250 MPO chr17 -0.1857 NM_000088 COL1A1 chr17 -0.1714 NM_000638 VTN chr17 -0.1646 NM_001184992 RNF135 chr17 -0.1601 NM_003954 MAP3K14 chr17 -0.1589 NM_006311 NCOR1 chr17 -0.1582 NM_000212 ITGB3 chr17 -0.1554 NM_004502 HOXB7 chr17 -0.1480 NM_018955 UBB chr17 -0.1462 NR_037772 CRHR1 chr17 -0.1389 NM_021137 TNFAIP1 chr17 -0.1389 NM_024015 HOXB4 chr17 -0.1389 NM_001126117 TP53 chr17 -0.1234 NM_002945 RPA1 chr17 -0.0929 NM_012448 STAT5B chr17 -0.0929 NM_002983 CCL3 chr17 -0.0929 NM_015077 SARM1 chr17 -0.0855 NM_183232 IKZF3 chr17 -0.0855 NM_003809 TNFSF12 chr17 -0.0855 NM_032963 CCL14 chr17 -0.0855 NM_002798 PSMB6 chr17 -0.0563 NM_001212 C1QBP chr17 -0.0563 NM_002986 CCL11 chr17 -0.0563 NM_002984 CCL4 chr17 -0.0563 NM_003110 SP2 chr17 -0.0563 NM_001838 CCR7 chr17 -0.0475 NM_002311 LIG3 chr17 -0.0293 NM_024119 DHX58 chr17 -0.0249 NM_203506 GRB2 chr17 -0.0216 NM_015716 MINK1 chr17 -0.0109 NM_001042422 SLC16A3 chr17 0.0190 NM_001678 ATP1B2 chr17 0.0212 NM_000346 SOX9 chr17 0.0314 NM_139034 MAPK7 chr17 0.0397 NM_199242 UNC13D chr17 0.0442 NM_021724 NR1D1 chr17 0.0516 NM_001075099 SKAP1 chr17 0.0756 NM_004774 MED1 chr17 0.1036 NM_198175 NME1 chr17 0.1067 NM_145109 MAP2K3 chr17 0.1242 NM_002795 PSMB3 chr17 0.1371 NM_005474 HDAC5 chr17 0.1371 NM_001099788 ICAM2 chr17 0.1371 NM_002204 ITGA3 chr17 0.1506 NM_001454 FOXJ1 chr17 0.1509 NM_002758 MAP2K6 chr17 0.1553 NM_174871 PSMD12 chr17 0.2039 NM_002982 CCL2 chr17 0.2178 NM_004313 ARRB2 chr17 0.2526 NM_002737 PRKCA chr17 0.2563 NM_014726 TBKBP1 chr17 0.2958 NM_002663 PLD2 chr17 0.4409 NM_172088 TNFSF13 chr17 0.4872 NM_199139 XAF1 chr17 0.5061 NM_006137 CD7 chr17 0.8504 NM_003593 FOXN1 chr17 1.3465 NM_003839 TNFRSF11A chr18 -0.3293 NM_000633 BCL2 chr18 -0.2960 NM_021127 PMAIP1 chr18 -0.2332 NM_001025101 MBP chr18 -0.2167 NM_004028 AQP4 chr18 -0.1967 NM_130386 COLEC12 chr18 -0.1423 NM_017831 RNF125 chr18 -0.1112 NM_001207013 PTPN2 chr18 -0.1038 NM_002647 PIK3C3 chr18 -0.0855 NM_006785 MALT1 chr18 -0.0183 NM_020648 TWSG1 chr18 0.2220 NM_005433 YES1 chr18 0.5030 NM_144662 PSMA8 chr18 0.6453 NM_001972 ELANE chr19 -0.9860 NM_001405 EFNA2 chr19 -0.8801 NM_002777 PRTN3 chr19 -0.8768 NM_001199216 MAG chr19 -0.8604 NM_172140 IL29 chr19 -0.8143 NM_032855 HSH2D chr19 -0.8127 NM_001100122 SBNO2 chr19 -0.7496 NM_005317 GZMM chr19 -0.7395 NM_006847 LILRB4 chr19 -0.6803 NM_001928 CFD chr19 -0.6273 NM_015868 KIR2DL3 chr19 -0.6213 NM_002812 PSMD8 chr19 -0.5977 NM_021250 LILRA5 chr19 -0.5824 NM_004368 CNN2 chr19 -0.5092 NM_001201359 CCL25 chr19 -0.4912 NM_003807 TNFSF14 chr19 -0.4910 NM_004069 AP2S1 chr19 -0.4772 NM_007121 NR1H2 chr19 -0.4624 NM_021175 HAMP chr19 -0.4530 NM_001242356 NCR1 chr19 -0.4358 NM_002255 KIR2DL4 chr19 -0.4332 NM_001700 AZU1 chr19 -0.4297 NM_006563 KLF1 chr19 -0.4234 NM_001083899 GP6 chr19 -0.4189 NM_001077523 AP3D1 chr19 -0.4090 NM_001294 CLPTM1 chr19 -0.4057 NM_001136019 FCGRT chr19 -0.4011 NM_000215 JAK3 chr19 -0.3962 NM_002162 ICAM3 chr19 -0.3860 NM_001126335 SLC7A9 chr19 -0.3814 NM_001144899 CD209 chr19 -0.3703 NM_006864 LILRB3 chr19 -0.3671 NM_138330 ZNF675 chr19 -0.3355 NM_032152 PRAM1 chr19 -0.3232 NM_001146206 RASGRP4 chr19 -0.3185 NM_001173515 TYROBP chr19 -0.3080 NM_014209 ETV2 chr19 -0.3052 NM_002002 FCER2 chr19 -0.2881 NM_021913 AXL chr19 -0.2657 NM_005809 PRDX2 chr19 -0.2654 NM_001204503 FLT3LG chr19 -0.2609 NM_014383 ZBTB32 chr19 -0.2136 NM_182919 TICAM1 chr19 -0.2117 NM_006221 PIN1 chr19 -0.2117 NM_202001 ERCC1 chr19 -0.2117 NM_004364 CEBPA chr19 -0.2094 NM_005091 PGLYRP1 chr19 -0.2051 NM_005755 EBI3 chr19 -0.1857 NM_198591 BSG chr19 -0.1759 NM_001252 CD70 chr19 -0.1693 NM_001130867 ERCC2 chr19 -0.1554 NM_003333 UBA52 chr19 -0.1522 NM_006332 IFI30 chr19 -0.1499 NM_000234 LIG1 chr19 -0.1480 NM_002229 JUNB chr19 -0.1480 NM_153701 IL12RB1 chr19 -0.1480 NM_001375 DNASE2 chr19 -0.1389 NM_001130524 AP1M1 chr19 -0.1389 NM_005428 VAV1 chr19 -0.1188 NM_001135768 PVR chr19 -0.1188 NM_001080978 LILRB2 chr19 -0.1145 NM_145185 MAP2K7 chr19 -0.1009 NM_004843 IL27RA chr19 -0.0929 NM_001736 C5AR1 chr19 -0.0929 NM_199054 MKNK2 chr19 -0.0855 NM_022377 ICAM4 chr19 -0.0855 NM_005178 BCL3 chr19 -0.0855 NM_003407 ZFP36 chr19 -0.0734 NM_021601 CD79A chr19 -0.0563 NM_013289 KIR3DL1 chr19 -0.0544 NM_001816 CEACAM8 chr19 -0.0319 NM_130760 MADCAM1 chr19 0.0103 NM_001197124 IRF3 chr19 0.0182 NM_002743 PRKCSH chr19 0.0394 NM_002856 PVRL2 chr19 0.0651 NM_019849 SLC7A10 chr19 0.0705 NM_006737 KIR3DL2 chr19 0.0760 NM_000064 C3 chr19 0.0807 NM_020406 CD177 chr19 0.0899 NM_030662 MAP2K2 chr19 0.0918 NM_000660 TGFB1 chr19 0.1213 NM_015898 ZBTB7A chr19 0.1371 NM_004335 BST2 chr19 0.1371 NM_002503 NFKBIB chr19 0.1371 NM_001207042 PRMT1 chr19 0.1371 NM_002250 KCNN4 chr19 0.1461 NM_212550 BLOC1S3 chr19 0.1553 NM_001195733 PIP5K1C chr19 0.1824 NM_006509 RELB chr19 0.1987 NM_133269 FCAR chr19 0.2397 NM_005860 FSTL3 chr19 0.2483 NM_000201 ICAM1 chr19 0.2621 NM_014257 CLEC4M chr19 0.2682 NM_001127396 STXBP2 chr19 0.2764 NM_003775 S1PR4 chr19 0.3085 NM_014218 KIR2DL1 chr19 0.3707 NM_001142465 ECSIT chr19 0.3749 NM_005027 PIK3R2 chr19 0.3793 NM_003811 TNFSF9 chr19 0.3871 NM_001806 CEBPG chr19 0.3871 NM_014266 HCST chr19 0.3871 NM_001025160 CD97 chr19 0.3991 NM_016270 KLF2 chr19 0.3991 NM_005498 AP1M2 chr19 0.4749 NM_052890 PGLYRP2 chr19 0.5698 NM_000641 IL11 chr19 0.5928 NM_003200 TCF3 chr19 0.6667 NM_015985 ANGPT4 chr20 -0.6591 NM_000744 CHRNA4 chr20 -0.5325 NM_000114 EDN3 chr20 -0.4652 NM_005194 CEBPB chr20 -0.3911 NM_001199786 FKBP1A chr20 -0.3751 NM_003650 CST7 chr20 -0.3203 NM_001160417 ZBP1 chr20 -0.3173 NM_006404 PROCR chr20 -0.2742 NM_004139 LBP chr20 -0.2632 NM_139074 DEFB127 chr20 -0.2577 NM_199144 UBE2V1 chr20 -0.2324 NM_002827 PTPN1 chr20 -0.2043 NM_005417 SRC chr20 -0.1981 NM_006814 PSMF1 chr20 -0.1813 NM_000361 THBD chr20 -0.1480 NM_020820 PREX1 chr20 -0.1418 NM_183079 PRNP chr20 -0.1038 NM_020746 MAVS chr20 -0.0855 NM_001242539 NCOA6 chr20 -0.0855 NM_002792 PSMA7 chr20 -0.0855 NM_031483 ITCH chr20 -0.0568 NM_005461 MAFB chr20 -0.0563 NM_173091 NFATC2 chr20 -0.0277 NM_012072 CD93 chr20 -0.0091 NM_015192 PLCB1 chr20 0.0406 NM_002660 PLCG1 chr20 0.0516 NM_152854 CD40 chr20 0.0565 NM_015474 SAMHD1 chr20 0.1371 NM_000214 JAG1 chr20 0.1766 NM_001191 BCL2L1 chr20 0.1886 NM_001040023 SIRPA chr20 0.2671 NM_006462 RBCK1 chr20 0.3702 NM_006466 POLR3F chr20 0.3991 NM_006192 PAX1 chr20 0.4273 NM_032107 L3MBTL1 chr20 0.6202 NM_017806 LIME1 chr20 0.6896 NM_001077490 GNAS chr20 0.9965 NM_005534 IFNGR2 chr21 -0.9533 NM_000383 AIRE chr21 -0.8641 NM_006272 S100B chr21 -0.7103 NM_004571 PKNOX1 chr21 -0.4038 NM_002463 MX2 chr21 -0.2337 NM_021219 JAM2 chr21 -0.1480 NM_018961 UBASH3A chr21 -0.1480 NM_001178046 MX1 chr21 -0.0855 NM_000628 IL10RB chr21 -0.0563 NM_000874 IFNAR2 chr21 0.0442 NM_201413 APP chr21 0.1371 NM_015259 ICOSLG chr21 0.2481 NM_001207063 CXADR chr21 0.2497 NM_000454 SOD1 chr21 0.2741 NM_000211 ITGB2 chr21 0.5241 NM_019601 SUSD2 chr22 -1.4657 NM_001193289 APOBEC3A chr22 -1.3339 NM_002133 HMOX1 chr22 -0.5474 NM_017414 USP18 chr22 -0.5462 NM_145912 NFAM1 chr22 -0.4755 NM_016272 TOB2 chr22 -0.4575 NM_002608 PDGFB chr22 -0.3781 NM_007128 VPREB1 chr22 -0.3568 NM_014323 PATZ1 chr22 -0.2960 NM_001127 AP1B1 chr22 -0.2666 NM_153497 TAB1 chr22 -0.2621 NM_021574 BCR chr22 -0.2493 NM_052945 TNFRSF13C chr22 -0.2303 NM_002745 MAPK1 chr22 -0.2256 NM_001136541 APOL1 chr22 -0.2244 NM_145298 APOBEC3F chr22 -0.2183 NM_006440 TXNRD2 chr22 -0.2105 NM_002309 LIF chr22 -0.1784 NM_013430 GGT1 chr22 -0.1626 NM_013356 SLC16A8 chr22 -0.1042 NR_036556 ANKRD54 chr22 -0.0563 NM_021822 APOBEC3G chr22 -0.0563 NM_005368 MB chr22 -0.0427 NM_000675 ADORA2A chr22 0.0376 NM_003678 THOC5 chr22 0.0442 NM_152855 IGLL1 chr22 0.0516 NM_001079539 XBP1 chr22 0.0786 NM_013416 NCF4 chr22 0.1304 NM_020530 OSM chr22 0.1371 NM_002473 MYH9 chr22 0.1371 NM_138338 POLR3H chr22 0.1371 NM_152237 GAS2L1 chr22 0.1415 NM_002415 MIF chr22 0.2621 NM_002751 MAPK11 chr22 0.2621 NM_148175 PPIL2 chr22 0.2768 NM_001082579 RBFOX2 chr22 0.3991 NM_005207 CRKL chr22 0.5241 NM_002049 GATA1 chrX -0.5223 NM_138636 TLR8 chrX -0.3810 NM_014009 FOXP3 chrX -0.3634 NM_003254 TIMP1 chrX -0.3494 NM_003916 AP1S2 chrX -0.1480 NM_001145252 CFP chrX -0.0855 NM_000425 L1CAM chrX -0.0855 NM_001163278 ODZ1 chrX -0.0563 NM_000377 WAS chrX -0.0019 NM_001130860 HEPH chrX 0.0807 NM_005044 PRKX chrX 0.1371 NM_001100431 VSIG4 chrX 0.1371 NM_000052 ATP7A chrX 0.2621 NM_181777 UBE2A chrX 0.2621 NM_181673 OGT chrX 0.5241 NM_017416 IL1RAPL2 chrX 0.7354 NM_001144886 CITED1 chrX 0.9112 NM_006579 EBP chrX 0.9232 NM_002444 MSN chrX 0.9284 NM_001551 IGBP1 chrX 1.0523 NM_024528 NKAP chrX 1.4814 NM_001399 EDA chrX 1.5000 NM_000116 TAZ chrX 1.6164 NM_170750 PSMD10 chrX 1.6426 NM_152787 TAB3 chrX 1.7903 NM_001081573 GAB3 chrX 1.8148 NM_004429 EFNB1 chrX 1.8770 NM_005229 ELK1 chrX 1.9569 NM_001164619 GPC3 chrX 1.9928 NM_017413 APLN chrX 2.0696 NM_002436 MPP1 chrX 2.1068 NM_000194 HPRT1 chrX 2.3173 NM_006521 TFE3 chrX 2.3790 NR_024450 BCAP31 chrX 2.4782 NM_001042351 G6PD chrX 2.8913 NM_001569 IRAK1 chrX 2.9617 NM_004586 RPS6KA3 chrX 3.1774 NM_001127197 ELF4 chrX 3.3991 NM_001145255 IKBKG chrX 3.6860 NM_001136157 OTUD5 chrX 4.1870 NM_013230 CD24 chrY 0.2272

< Example 3>

Naive CD4 ⁺ Of T cells and control DNA methylation compare

Methylation was compared using primer pairs of genes showing a specific methylation tendency in psoriasis patients.

2ug of DNA from Naive CD4+ T cells of 3 healthy adults and 3 psoriasis patients was cut using MseI (NEB) restriction enzyme and overnight at 37°C. After purifying each DNA using the QIAquick PCR Purification Kit (QIAGEN), only methylated DNA is obtained using the methylcollector kit (Active Motif, USA). The test method followed manufacturers' protocols described in the Methylcollector kit (Active Motif, USA). Each DNA obtained through the methylcollector kit was amplified by HotStarTaq Polymerase (Qiagen, USA). The first cycle was at 95℃ for 10 minutes, then at 95℃ for 1 minute, 64℃ for 1 minute, and 72℃ for 1 minute. Repeated 37 times. Finally, after standing at 72°C for 10 minutes, the results were confirmed using 1% agarose gel. The primers and PCR product sizes used in each PCR are shown in [Table 4].

Gene name Sequence and sequence number product size SLITRK4 5'-TGCCGAGCGCTAGCAAT-3' (SEQ ID NO: 1)
5'-TCATGCCGCTGAGGACC-3' (SEQ ID NO: 2) 251 bp EMD 5'-CCTCGCGTTGATGACGTT-3' (SEQ ID NO: 3)
5'-GGTGGTCAGCTCGGTATCC-3' (SEQ ID NO: 4) 342 bp ZIC3 5'-AGTTCCCCGCAGCCACTC -3' (SEQ ID NO: 5)
5'-GCGAGTCCCAGCCTCTTC-3' (SEQ ID NO: 6) 318 bp CXorf40A 5'-TTGCAGCCTGGACACTAGC-3' (SEQ ID NO: 7)
5'-CCAGCCCTCAGGTACCGT-3' (SEQ ID NO: 8) 281 bp

As a result, as shown in [Fig. 4], it was confirmed that the methylation level of the gene promoter of the present invention is significantly higher in the psoriasis patient group than in the normal person.

Accordingly, the present invention provides a method for detecting methylation of a promoter of a gene located on the X chromosome to provide information necessary for the diagnosis of psoriasis, and a composition for diagnosis of psoriasis comprising an agent capable of measuring the methylation level. The method and composition of the present invention can provide genetic information in the diagnosis of psoriasis skin diseases, and thus are effective in diagnosing psoriasis, and thus have great industrial applicability.

<110> catholic univ. <120> Composition for diagnosing psoriasis <130> 12-0004 <160> 10 <170> KopatentIn 2.0 <210> 1 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> primer for SLITRK4 <400> 1 tgccgagcgc tagcaat 17 <210> 2 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> primer for SLITRK4 <400> 2 tcatgccgct gaggacc 17 <210> 3 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer for EMD <400> 3 cctcgcgttg atgacgtt 18 <210> 4 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> primer for EMD <400> 4 ggtggtcagc tcggtatcc 19 <210> 5 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer for ZIC3 <400> 5 agttccccgc agccactc 18 <210> 6 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer for ZIC3 <400> 6 gcgagtccca gcctcttc 18 <210> 7 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> primer for CXorf40A <400> 7 ttgcagcctg gacactagc 19 <210> 8 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer for CXorf40A <400> 8 ccagccctca ggtaccgt 18 <210> 9 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> linker primer for upper strand sequence <400> 9 tagaattcag atctcccg 18 <210> 10 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> linker primer for lower strand sequence <400> 10 cttaagtcta gagggcccag tggcg 25

Claims (13)

To provide information necessary for psoriasis diagnosis
(a) measuring the methylation level of the promoter of the emerin (Homo sapiens emerin, EMD: GenBank Accession No. NM_000117) gene located on the X chromosome from the target sample; And
(b) comparing the degree of methylation of said promoter with the methylation level of the same promoter of a normal control sample.
A method for detecting hypermethylation of the promoter of the emerin (Homo sapiens emerin, EMD: GenBank Accession No. NM_000117) gene located on the X chromosome.
3. The method according to claim 1, wherein the gene located on the X chromosome is selected from the group consisting of LOC339822 (GenBank Accession No. NR_033880), FKBP6 (GenBank Accession No. NM_003602), TRIM50 (GenBank Accession No. NM_178125), ABCD1 (GenBank Accession No. NM_000033) (GenBank Accession No. NM_000194), PHKA2 (GenBank Accession No. NM_000292), G6PD (GenBank Accession No. NM_000402), NR0B1 (GenBank Accession No. NM_000475), RPL39 (GenBank Accession No. NM_001000), MAP3K15 (GenBank Accession No. NM_000194). (GenBank Accession No. NM_001008222), KIAA2022 (GenBank Accession No. NM_001008537), DNASE1L1 (GenBank Accession No. NM_001009934), ZMAT1 (GenBank Accession No. NM_001011657), NHSL2 (GenBank Accession No. NM_001013627), DCAF12L2 GenBank Accession No. NM_001013628), CXorf40B (GenBank Accession No. NM_001013845), VMA21 (GenBank Accession No. NM_001017980), RGAG4 (GenBank Accession No. NM_001024455), LONRF3 (GenBank Accession No. NM_001031855), SCML1 (GenBank Accession No. NM_001037540 ), PRPS2 (GenBank Accession No. NM_001039 091), GPRASP1 (GenBank Accession No. NM_001099411), MAGIX (GenBank Accession No. (GenBank Accession No. NM_001107876), ANKRD58 (GenBank Accession No. NM_001105576), MECP2 (GenBank Accession No. NM_001110792), CASK (GenBank Accession No. NM_001126054), ELF4 (GenBank Accession No. NM_001127197), CLCN5 (GenBank Accession No. NM_001127899), FAM58A GenBank Accession No. NM_001130997), FAM127B (GenBank Accession No. NM_001134321), PNCK (GenBank Accession No. NM_001135740), NDUFB11 (GenBank Accession No. NM_001135998), OTUD5 (GenBank Accession No. NM_001136157), BCAP31 (GenBank Accession No. NM_001139441 ), PDK3 (GenBank Accession No. NM_001142386), DKC1 (GenBank Accession No. NM_001142463), IKBKG (GenBank Accession No. NM_001145255), FHL1 (GenBank Accession No. NM_001159703), FAM104B (GenBank Accession No. NM_001166704), MAP7D2 Accession No. NM_001168465), CNKSR2 (GenBank Accession No. NM_001168649), AFF2 (GenBank Accession No. NM_001169124), CXorf58 (GenBank Accession No. NM_001169574), MBNL3 (GenBank Accession No. NM_001170704), SRPX (GenBank Accession No. NM_001170750) , CXorf40A (GenBank Accession No. NM TMEM185A (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_001174092), MJLD1 (GenBank Accession No. NM_001177465), PPP1R3F (GenBank Accession No. NM_001184745), SLITRK4 (GenBank Accession No. NM_001184750), PHF8 (GenBank Accession No. NM_001184898), MSL3 GenBank Accession No. NM_001204467), DUSP9 (GenBank Accession No. NM_001395), GPC4 (GenBank Accession No. NM_001448), GDI1 (GenBank Accession No. NM_001493), IL13RA1 (GenBank Accession No. NM_001560), IRAK1 (GenBank Accession No. NM_001569 ), SHROOM2 (GenBank Accession No. NM_001649), MPP1 (GenBank Accession No. NM_002436), SUV39H1 (GenBank Accession No. NM_003173), ZIC3 (GenBank Accession No. NM_003413), IRS4 (GenBank Accession No. NM_003604), FGF13 Accession No. NM_004114), IDH3G (GenBank Accession No. NM_004135), NDUFA1 (GenBank Accession No. NM_004541), RPS6KA3 (GenBank Accession No. NM_004586), RAB33A (GenBank Accession No. NM_004794) , SOX3 (GenBank Accession No. NM_005634), PQBP1 (GenBank Accession No. NM_005710), RPL10 (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_006513), PRICKLE3 (GenBank Accession No. NM_006150), SSR4 (GenBank Accession No. NM_006280), SLC16A2 (GenBank Accession No. NM_006517), TFE3 (GenBank Accession No. NM_006521), RBM3 GenBank Accession No. NM_006743), RNF113A (GenBank Accession No. NM_006978), WDR45 (GenBank Accession No. NM_007075), ZNF41 (GenBank Accession No. NM_007130), FTSJ1 (GenBank Accession No. NM_012280), PNMA3 (GenBank Accession No. NM_013364 ), UBL4A (GenBank Accession No. NM_014235), RPS6KA6 (GenBank Accession No. NM_014496), HTATSF1 (GenBank Accession No. NM_014500), PHF16 (GenBank Accession No. NM_014735), FAM155B (GenBank Accession No. NM_015686), WWC3 Accession No. NM_015691), APLN (GenBank Accession No. NM_017413), PLXNA3 (GenBank Accession No. NM_017514), NUDT11 (GenBank Accession No. NM_018159), GABRQ (GenBank Accession No. NM_018558), SLC10A3 (GenBank Accession No. NM_019848) , PCDH19 (GenBank Accession No. NM_020766), WNK3 (GenBank Accession No. NM_020922), XK (GenBank Acces sion No. (GenBank Accession No. NM_021083), FAM3A (GenBank Accession No. NM_021806), TMEM47 (GenBank Accession No. NM_031442), CD99L2 (GenBank Accession No. NM_031462), SH3KBP1 (GenBank Accession No. NM_031892), PDZD4 (GenBank Accession No. NM_032512), SLC9A7 GenBank Accession No. NM_032591), DACH2 (GenBank Accession No. NM_053281), SYN1 (GenBank Accession No. NM_133499), DOCK11 (GenBank Accession No. NM_144658), FAM123B (GenBank Accession No. NM_152424), KLHL34 (GenBank Accession No. NM_153270 ), PTCHDl (GenBank Accession No. NM_173495), DCAF12L1 (GenBank Accession No. NM_178470), UBE2A (GenBank Accession No. NM_181762), LINC00086 (GenBank Accession No. NR_024359), LINC00087 (GenBank Accession No. NR_024493) Accession No. NR_026545), LOC158572 (GenBank Accession No. NR_026742), LOC100272228 (GenBank Accession No. NR_027456), LOC100303728 (GenBank Accession No. NR_028443), MIR718 (GenBank Accession No. NR_031757), RAI2 (GenBank Accession No. NR_033348) , SCML2 (GenBank Accession No. NR_033717), LOC100129662 (GenBank Accession No. Methylation of a promoter of a gene located on at least one X chromosome selected from the group consisting of LOC100506757 (NR_038405), and LOC100506757 (GenBank Accession No. NR_038998).
The method according to claim 1, wherein hypermethylation of a promoter of a gene located on at least one X chromosome selected from the group consisting of SLITRK4 (GenBank Accession No. NM_001184750), ZIC3 (GenBank Accession No. NM_003413) and CXorf40A (GenBank Accession No. NM_001171908) Lt; RTI ID = 0.0 &gt; additionally &lt; / RTI &gt;
The method according to claim 1, wherein the target sample is at least one selected from the group consisting of psoriasis suspect patients, tissues derived from a diagnosis subject, cells, blood and urine.
5. The method of claim 4, wherein the cell is a non-contact T cell.
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, PCR, quantitative PCR, pyrosequencing, and bisulfite sequencing. &Lt; Desc / Clms Page number 13 &gt;
A composition for the diagnosis of psoriasis, which comprises an agent for measuring the hypermethylation level of the promoter of the emerin (Homo sapiens emerin, EMD: GenBank Accession No. NM_000117) gene located on the X chromosome.
9. The method according to claim 7, wherein the LBP is selected from the group consisting of LOC339822 (GenBank Accession No. NR_033880), FKBP6 (GenBank Accession No. NM_003602), TRIM50 (GenBank Accession No. NM_178125), ABCD1 (GenBank Accession No. NM_000033), HPRT1 (GenBank Accession No. NM_000194) , GenBank Accession No. NM_000292), G6PD (GenBank Accession No. NM_000402), NR0B1 (GenBank Accession No. NM_000475), RPL39 (GenBank Accession No. NM_001000), MAP3K15 (GenBank Accession No. NM_001001671), ZDHHC9 GenBank Accession No. NM_001013628), GenBank Accession No. NM_001013628, GenBank Accession No. NM_001013628, GenBank Accession No. NM_001013628), KIAA2022 (GenBank Accession No. NM_001008537), DNASE1L1 (GenBank Accession No. NM_001009934), ZMAT1 (GenBank Accession No. NM_001013845), VMA21 (GenBank Accession No. NM_001017980), RGAG4 (GenBank Accession No. NM_001024455), LONRF3 (GenBank Accession No. NM_001031855), SCML1 (GenBank Accession No. NM_001037540), PRPS2 , NM_001039091), GPRASP1 (GenBank Accession No. NM_001099 411), MAGIX (GenBank Accession No. 2). (GenBank Accession No. NM_001107876), ANKRD58 (GenBank Accession No. NM_001105576), MECP2 (GenBank Accession No. NM_001110792), CASK (GenBank Accession No. NM_001126054), ELF4 (GenBank Accession No. NM_001127197), CLCN5 (GenBank Accession No. NM_001127899), FAM58A GenBank Accession No. NM_001130997), FAM127B (GenBank Accession No. NM_001134321), PNCK (GenBank Accession No. NM_001135740), NDUFB11 (GenBank Accession No. NM_001135998), OTUD5 (GenBank Accession No. NM_001136157), BCAP31 (GenBank Accession No. NM_001139441 ), PDK3 (GenBank Accession No. NM_001142386), DKC1 (GenBank Accession No. NM_001142463), IKBKG (GenBank Accession No. NM_001145255), FHL1 (GenBank Accession No. NM_001159703), FAM104B (GenBank Accession No. NM_001166704), MAP7D2 Accession No. NM_001168465), CNKSR2 (GenBank Accession No. NM_001168649), AFF2 (GenBank Accession No. NM_001169124), CXorf58 (GenBank Accession No. NM_001169574), MBNL3 (GenBank Accession No. NM_001170704), SRPX (GenBank Accession No. NM_001170750) , CXorf40A (GenBank Accession No. NM TMEM185A (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_001174092), MJLD1 (GenBank Accession No. NM_001177465), PPP1R3F (GenBank Accession No. NM_001184745), SLITRK4 (GenBank Accession No. NM_001184750), PHF8 (GenBank Accession No. NM_001184898), MSL3 GenBank Accession No. NM_001204467), DUSP9 (GenBank Accession No. NM_001395), GPC4 (GenBank Accession No. NM_001448), GDI1 (GenBank Accession No. NM_001493), IL13RA1 (GenBank Accession No. NM_001560), IRAK1 (GenBank Accession No. NM_001569 ), SHROOM2 (GenBank Accession No. NM_001649), MPP1 (GenBank Accession No. NM_002436), SUV39H1 (GenBank Accession No. NM_003173), ZIC3 (GenBank Accession No. NM_003413), IRS4 (GenBank Accession No. NM_003604), FGF13 Accession No. NM_004114), IDH3G (GenBank Accession No. NM_004135), NDUFA1 (GenBank Accession No. NM_004541), RPS6KA3 (GenBank Accession No. NM_004586), RAB33A (GenBank Accession No. NM_004794) , SOX3 (GenBank Accession No. NM_005634), PQBP1 (GenBank Accession No. NM_005710), RPL10 (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_006513), PRICKLE3 (GenBank Accession No. NM_006150), SSR4 (GenBank Accession No. NM_006280), SLC16A2 (GenBank Accession No. NM_006517), TFE3 (GenBank Accession No. NM_006521), RBM3 GenBank Accession No. NM_006743), RNF113A (GenBank Accession No. NM_006978), WDR45 (GenBank Accession No. NM_007075), ZNF41 (GenBank Accession No. NM_007130), FTSJ1 (GenBank Accession No. NM_012280), PNMA3 (GenBank Accession No. NM_013364 ), UBL4A (GenBank Accession No. NM_014235), RPS6KA6 (GenBank Accession No. NM_014496), HTATSF1 (GenBank Accession No. NM_014500), PHF16 (GenBank Accession No. NM_014735), FAM155B (GenBank Accession No. NM_015686), WWC3 Accession No. NM_015691), APLN (GenBank Accession No. NM_017413), PLXNA3 (GenBank Accession No. NM_017514), NUDT11 (GenBank Accession No. NM_018159), GABRQ (GenBank Accession No. NM_018558), SLC10A3 (GenBank Accession No. NM_019848) , PCDH19 (GenBank Accession No. NM_020766), WNK3 (GenBank Accession No. NM_020922), XK (GenBank Acces sion No. (GenBank Accession No. NM_021083), FAM3A (GenBank Accession No. NM_021806), TMEM47 (GenBank Accession No. NM_031442), CD99L2 (GenBank Accession No. NM_031462), SH3KBP1 (GenBank Accession No. NM_031892), PDZD4 (GenBank Accession No. NM_032512), SLC9A7 GenBank Accession No. NM_032591), DACH2 (GenBank Accession No. NM_053281), SYN1 (GenBank Accession No. NM_133499), DOCK11 (GenBank Accession No. NM_144658), FAM123B (GenBank Accession No. NM_152424), KLHL34 (GenBank Accession No. NM_153270 ), PTCHDl (GenBank Accession No. NM_173495), DCAF12L1 (GenBank Accession No. NM_178470), UBE2A (GenBank Accession No. NM_181762), LINC00086 (GenBank Accession No. NR_024359), LINC00087 (GenBank Accession No. NR_024493) Accession No. NR_026545), LOC158572 (GenBank Accession No. NR_026742), LOC100272228 (GenBank Accession No. NR_027456), LOC100303728 (GenBank Accession No. NR_028443), MIR718 (GenBank Accession No. NR_031757), RAI2 (GenBank Accession No. NR_033348) , SCML2 (GenBank Accession No. NR_033717), LOC100129662 (GenBank Accession No. NR_038405), and LOC100506757 (GenBank Accession No. NR_038998), wherein the promoter of the promoter of one or more genes located on the X chromosome is further measured.
The method according to claim 7, wherein the promoter of one or more genes located on the X chromosome selected from the group consisting of SLITRK4 (GenBank Accession No. NM_001184750), ZIC3 (GenBank Accession No. NM_003413) and CXorf40A (GenBank Accession No. NM_001171908) Lt; RTI ID = 0.0 &gt; of: &lt; / RTI &gt;
10. The composition according to any one of claims 7 to 9, wherein the agent for measuring the hypermethylation level of the promoter of the gene comprises a primer that specifically binds to the gene.
11. The composition according to claim 10, wherein the primer specifically binding to the gene is a primer selected from the group consisting of primers represented by SEQ ID NOS: 1 to 8.
A kit for psoriasis diagnosis comprising an agent for measuring the hypermethylation level of a promoter of an emerin (Homo sapiens emerin, EMD: GenBank Accession No. NM_000117) gene located on the X chromosome.
13. The method according to claim 12, wherein LOC339822 (GenBank Accession No. NR_033880), FKBP6 (GenBank Accession No. NM_003602), TRIM50 (GenBank Accession No. NM_178125), ABCD1 (GenBank Accession No. NM_000033), HPRT1 (GenBank Accession No. NM_000194) , GenBank Accession No. NM_000292), G6PD (GenBank Accession No. NM_000402), NR0B1 (GenBank Accession No. NM_000475), RPL39 (GenBank Accession No. NM_001000), MAP3K15 (GenBank Accession No. NM_001001671), ZDHHC9 GenBank Accession No. NM_001013628), GenBank Accession No. NM_001013628, GenBank Accession No. NM_001013628, GenBank Accession No. NM_001013628), KIAA2022 (GenBank Accession No. NM_001008537), DNASE1L1 (GenBank Accession No. NM_001009934), ZMAT1 (GenBank Accession No. NM_001013845), VMA21 (GenBank Accession No. NM_001017980), RGAG4 (GenBank Accession No. NM_001024455), LONRF3 (GenBank Accession No. NM_001031855), SCML1 (GenBank Accession No. NM_001037540), PRPS2 , NM_001039091), GPRASP1 (GenBank Accession No. NM_00109 9411), MAGIX (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_001107876), ANKRD58 (GenBank Accession No. NM_001105576), MECP2 (GenBank Accession No. NM_001110792), CASK (GenBank Accession No. NM_001126054), ELF4 (GenBank Accession No. NM_001127197), CLCN5 (GenBank Accession No. NM_001127899), FAM58A GenBank Accession No. NM_001130997), FAM127B (GenBank Accession No. NM_001134321), PNCK (GenBank Accession No. NM_001135740), NDUFB11 (GenBank Accession No. NM_001135998), OTUD5 (GenBank Accession No. NM_001136157), BCAP31 (GenBank Accession No. NM_001139441 ), PDK3 (GenBank Accession No. NM_001142386), DKC1 (GenBank Accession No. NM_001142463), IKBKG (GenBank Accession No. NM_001145255), FHL1 (GenBank Accession No. NM_001159703), FAM104B (GenBank Accession No. NM_001166704), MAP7D2 Accession No. NM_001168465), CNKSR2 (GenBank Accession No. NM_001168649), AFF2 (GenBank Accession No. NM_001169124), CXorf58 (GenBank Accession No. NM_001169574), MBNL3 (GenBank Accession No. NM_001170704), SRPX (GenBank Accession No. NM_001170750) , CXorf40A (GenBank Accession No. NM TMEM185A (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_001174092), MJLD1 (GenBank Accession No. NM_001177465), PPP1R3F (GenBank Accession No. NM_001184745), SLITRK4 (GenBank Accession No. NM_001184750), PHF8 (GenBank Accession No. NM_001184898), MSL3 GenBank Accession No. NM_001204467), DUSP9 (GenBank Accession No. NM_001395), GPC4 (GenBank Accession No. NM_001448), GDI1 (GenBank Accession No. NM_001493), IL13RA1 (GenBank Accession No. NM_001560), IRAK1 (GenBank Accession No. NM_001569 ), SHROOM2 (GenBank Accession No. NM_001649), MPP1 (GenBank Accession No. NM_002436), SUV39H1 (GenBank Accession No. NM_003173), ZIC3 (GenBank Accession No. NM_003413), IRS4 (GenBank Accession No. NM_003604), FGF13 Accession No. NM_004114), IDH3G (GenBank Accession No. NM_004135), NDUFA1 (GenBank Accession No. NM_004541), RPS6KA3 (GenBank Accession No. NM_004586), RAB33A (GenBank Accession No. NM_004794) , SOX3 (GenBank Accession No. NM_005634), PQBP1 (GenBank Accession No. NM_005710), RPL10 (GenBank Accession No. &lt; / RTI &gt; (GenBank Accession No. NM_006513), PRICKLE3 (GenBank Accession No. NM_006150), SSR4 (GenBank Accession No. NM_006280), SLC16A2 (GenBank Accession No. NM_006517), TFE3 (GenBank Accession No. NM_006521), RBM3 GenBank Accession No. NM_006743), RNF113A (GenBank Accession No. NM_006978), WDR45 (GenBank Accession No. NM_007075), ZNF41 (GenBank Accession No. NM_007130), FTSJ1 (GenBank Accession No. NM_012280), PNMA3 (GenBank Accession No. NM_013364 ), UBL4A (GenBank Accession No. NM_014235), RPS6KA6 (GenBank Accession No. NM_014496), HTATSF1 (GenBank Accession No. NM_014500), PHF16 (GenBank Accession No. NM_014735), FAM155B (GenBank Accession No. NM_015686), WWC3 Accession No. NM_015691), APLN (GenBank Accession No. NM_017413), PLXNA3 (GenBank Accession No. NM_017514), NUDT11 (GenBank Accession No. NM_018159), GABRQ (GenBank Accession No. NM_018558), SLC10A3 (GenBank Accession No. NM_019848) , PCDH19 (GenBank Accession No. NM_020766), WNK3 (GenBank Accession No. NM_020922), XK (GenBank Acces sion No. (GenBank Accession No. NM_021083), FAM3A (GenBank Accession No. NM_021806), TMEM47 (GenBank Accession No. NM_031442), CD99L2 (GenBank Accession No. NM_031462), SH3KBP1 (GenBank Accession No. NM_031892), PDZD4 (GenBank Accession No. NM_032512), SLC9A7 GenBank Accession No. NM_032591), DACH2 (GenBank Accession No. NM_053281), SYN1 (GenBank Accession No. NM_133499), DOCK11 (GenBank Accession No. NM_144658), FAM123B (GenBank Accession No. NM_152424), KLHL34 (GenBank Accession No. NM_153270 ), PTCHDl (GenBank Accession No. NM_173495), DCAF12L1 (GenBank Accession No. NM_178470), UBE2A (GenBank Accession No. NM_181762), LINC00086 (GenBank Accession No. NR_024359), LINC00087 (GenBank Accession No. NR_024493) Accession No. NR_026545), LOC158572 (GenBank Accession No. NR_026742), LOC100272228 (GenBank Accession No. NR_027456), LOC100303728 (GenBank Accession No. NR_028443), MIR718 (GenBank Accession No. NR_031757), RAI2 (GenBank Accession No. NR_033348) , SCML2 (GenBank Accession No. NR_033717), LOC100129662 (GenBank Accession No. NR_038405), and LOC100506757 (GenBank Accession No. NR_038998), wherein the hypermethylation level of the promoter of at least one gene located on the X chromosome is further measured.

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