KR101105811B1 - Biomarker for extrinsic type atopic dermatitis - Google Patents

Abstract

The present invention relates to a marker useful for diagnosing and / or treating exogenous atopic dermatological diseases. The present invention relates to a method for diagnosing exogenous atopic dermatological diseases using the same, and a method for detecting an inducing factor of exogenous atopic dermatological diseases by targeting the marker. Or methods for screening for the prevention, alleviation and / or treatment of exogenous atopic dermatological diseases.

Description

Biomarker for exogenous atopic dermatitis {BIOMARKER FOR EXTRINSIC TYPE ATOPIC DERMATITIS}

The present invention relates to a marker useful for diagnosing and / or treating exogenous atopic dermatological diseases. The present invention relates to a method for diagnosing exogenous atopic dermatological diseases using the same, and a method for detecting an inducing factor of exogenous atopic dermatological diseases by targeting the marker. Or methods for screening for the prevention, alleviation and / or treatment of exogenous atopic dermatological diseases.

Atopic dermatitis (AD) is caused by various factors such as genetic factors and environmental factors, and its mechanism is not clear. Symptoms include erythema, edema, severe pruritus, effusion, scab and scale, and the incidence rate is increasing year by year due to the development of industry, environmental pollution, dietary changes, and genetic factors. Currently, atopic dermatological diseases are diagnosed entirely by gross findings, and thus objectivity is lacking because subjective intervention by a clinician is involved.

Although various causes of atopic dermatitis are known, there is still a need to discover genes that cause the lack of accurate treatment and the complexity of diseases in the human body. In particular, it is a difficult task to determine the severity of the pidgin that determines the treatment among atopic skin diseases. In addition, since the general trend of avoiding steroid external preparations, which is a large pillar of the treatment of atopic dermatological diseases, is becoming stronger, development of appropriate treatment techniques is desired. Therefore, it is an important task to search for atopic dermatological markers that can classify the severity of atopic dermatological diseases as an indicator of worsening of the condition and an indication of the therapeutic effect.

In addition, due to the increase in the incidence of atopic dermatitis and serious problems with the quality of life, social attention is becoming so important that it is a national issue. It is time to develop a friendly treatment.

In this regard, attempts have been made through combining clinical and basic medicine, but there is a need for identification of changes occurring in more fundamental patient skin tissues and accurate and effective treatment based on them.

To this end, in the present invention, by combining techniques such as a gene chip analysis method, bioinformatics, etc., a successful discovery of a group of genes showing abnormal expression in an exogenous atopic skin disease patient, and finally selecting key proteins, the present invention Completed.

Thus, one embodiment of the present invention provides a marker for diagnosing atopic dermatological diseases selected from the group consisting of genes whose expression is increased or decreased in atopic dermatological patients and proteins encoded by the genes.

Another example of the present invention is an atopic skin disease capable of detecting the expression of an atopic dermatological diagnostic marker selected from the group consisting of a gene whose expression is increased or decreased in atopic skin disease patients and a protein encoded by the gene. Provide diagnostic chip.

Another embodiment of the present invention provides a method for diagnosing atopic dermatitis by measuring whether the expression of the atopic dermatitis diagnostic marker is increased or decreased.

Another example of the present invention provides a method for searching for atopic dermatitis inducing factors by measuring the expression level of the marker for diagnosing atopic dermatitis after treating a candidate with a sample.

Another example of the present invention provides a method of searching for a prophylactic and / or therapeutic substance for atopic dermatitis by measuring a degree of expression of the marker for diagnosing atopic dermatitis after treating a candidate with a sample.

When classified into exogenous and endogenous, the patients with exogenous atopic dermatitis occupy 70-80% of all patients. Therefore, by discovering genes that cause abnormal expression in exogenous patients, it is effective for diagnosis, treatment and personalization. I want to achieve medicine.

To this end, prior to the present invention, the present invention was divided into exogenous atopic dermatitis and endogenous atopic dermatitis. For the effective treatment and diagnosis of exogenous atopic dermatitis, 34K gene chips were used to select gene groups with specific expression differences in patients, and bioinformatics were used to identify key genes successfully.

Based on the experimental results of the gene chip, genes such as HNRPA2B1, KRT1, VDAC1, AKR1C2, CLIC1, BARD1, IFIT1, VIM, AHCY, ALDH1A1, BCL11A and C3 were selected, and FABP7, CPA3, ARSF, AREG , GJB2, GLTP, HAS3, HIST4H4, etc. were found to be markers of treatment. In addition, we combined heavy computer simulation with TNC, VCAM1, CXADR, CEACAM5, COL12A1, NTRK2, CTSG, CD200R1, KLK4, KLK6 , KLK8, KLK14, TMPRSS11D, PLAT, CDON, ACTG2, etc. were further excavated. These genes are the genes that can be used centrally in the treatment of exogenous atopic dermatitis.

The expression of genes in the patient's skin consists of genes that are abnormally more than doubled and those that are more than doubled compared to normal humans. Other key genes play central dynamics in the interaction of genes.

Hereinafter, the present invention will be described more specifically.

An example of the present invention provides a marker for diagnosing exogenous atopic skin disease selected from the group consisting of the following genes and proteins encoded by the genes:

POSTN (NM_006475), TNC (NM_002160), VCAM1 (NM_001078), COL1A1 (NM_000088), COL1A2 (NM_000089), COL3A1 (NM_000090), COL12A1 (NM_004370), COL15A1 (NM_001M_X) LOXL2 (NM_002318), NOV (NM_002514), MMP2 (NM_004530), MMP12 (NM_002426), DSC1 (NM_004948), CLDN10 (NM_006984), CXADR (NM_001338), COMP (NM_000095), CEACAM5 (NM_00363N) Extracellular matrix (ECM) and cell adhesion genes, including GJB2 (NM_004004), GJB6 (NM_006783), and the like;

Cytokine or chemokine related genes including CCL18 (NM_002988), CXCL14 (NM_004887), CD74 antigen (NM_001025158), IL1F9 (NM_019618), IFNA1 (NM_024013), AREG (NM_001657), IL1F6 (NM_014440), and the like;

CTSL2 (NM_001333), CTSG (NM_001911), DEFB4 (NM_004942), FceRI (NM_002001), CD1E (NM_030893), CD1A antigen (NM_001763), CD200R1 (NM_138806), MNDA (NM_002432), SPINK974N (NM_002432) Antimicrobial peptides and immune response genes, including IFI27 (NM_005532), CD97 (NM_001025160), PI3 (NM_002638), NFKBIZ (NM_001005474) and the like;

CPA3 (NM_001870), TPSAB1 (NG_005083), CST6 (NM_001323), CPVL (NM_019029), TMPRSS11D (NM_004262), KLK4 (NM_004917), KLK6 (NM_001012964), KLK8 (NM_007196__0), KLK14 (NMRP) Proteolytic enzymes or inhibitors thereof including SERPINB13 (NM_012397), SERPINB3 (NM_006919), PLAT (NM_000930), CSTA (NM_005213), SHH (NM_000193), PRSS3 (NG_001337), and USP11 (NM_004651) and the like;

THRSP (NM_003251), PLA2G4C (NM_003706), PLA2R1 (NM_001007267), Zn-alpha-2-GP (XM_379897), FADS2 (NM_004265), FABP7 (NM_001446), ANXA2 (NM_001002857), CRABPN (NM_001), NM_001 Lipid related genes, including GM2A (NM_000405), MAL (NM_002371), LDLR (NM_000527), GLTP (NM_016433), and the like;

MFI2 (NM_005929), RNF152 (NM_173557), RNF24 (NM_007219), SPARC (NM_003118), ZNF90 (M61870), ZNF117 (NM_024498), ZNF185 (NM_007150), SNAI2 (NM_003068), RCN3A (NM_020) (NM_020) ADAM9 (NM_001005845), TCN1 (NM_001062), S100A9 (NM_002965), SLC5A6 (NM_021095), SLC39A2 (NM_014579), TRIM16 (NM_006470), CANT1 (NM_138793), CACNB2 (NM_000_MN_0000) And metal binding genes including SPRR2C (NG_005086) and the like;

Hormone-related genes including MGB1 (NM_002411), PPARG (NM_005037), SULT1E1 (NM_005420), and the like;

NTRK2 (NM_001007097), NVL (NM_002533), PDK3 (NM_005391), SMMHC (NM_002474), PMCA4 (NM_001001396), GALK2 (NM_001001556), TRPM2 (NM_001001188), Tubulin (alpha 2 isoform 2), NM_01 036 And ATP or GTP binding genes including PHKG1 (NM_006213) and the like;

LCE2B (NM_014357), KRT18 (NM_000224), CDON (NM_016952), MAPRE2 (NM_014268), MRPS27 (NM_015084), AMBN (NM_016519), ACTG2 (NM_001615), DES (NM_001927), SSH1 (NM001001), M_T_001001M And structural genes including LMOD1 (NM_012134), MRPS18A (NM_018135), RPL10 (NM_006013), and the like;

Heparin binding genes including UST (NM_005715), PGF (NM_002632), HBEGF (NM_001945), FGFBP1 (NM_005130) and the like;

SOX9 (NM_000346), ID4 (NM_001546), HCLS1 (NM_005335), FOS (NM_005252), PITX2 (NM_000325), FOSB (NM_006732), MEIS1 (NM_002398), GRHL3 (NM_021180), HSF2BP (NM_00739), NM_007031 Transcription genes including the like;

SLC1A2 (NM_004171), SLC16A14 (NM_152527), KDELR3 (NM_006855), RHCG (NM_016321), SOSTDC1 (NM_015464), DARPP-32 (NM_032192), MGST1 (NM_020300), SLC7A5 (NM_003486), etc. Transport genes;

ADH1A (NM_000667), ST6GALNAC2 (NM_006456), BBOX1 (NM_003986), PYGL (NM_002863), SOAT1 (NM_003101), ARSF (NM_004042), TGM1 (NM_000359), AKR1B10 (NM_020293), NM_000C4R8, NM_0020399, NF_203203 Metabolic enzyme genes including FUT11 (NM_173540), HADHB (NM_000183), PPP1R12B (NM_002481), SFN (NM_006142), PGLYRP3 (NM_052891), BCKDHA (NM_000709), and the like;

Nucleic acid binding genes including ZNF664 (NM_152437), ZNF681 (NM_138286), EIF3S9 (NM_003751), MYOCD (NM_153604), HIST4H4 (NM_175054), and the like;

Receptor or binding genes including SFRP1 (NM_003012), F2R (NM_001992), FOLR2 (NM_000803), MUC4 (NM_004532), SEMA6C (NM_030913), KCTD18 (NM_152387), PDLIM7 (NM_005451), and the like; And

SNX16 (NM_022133), SESN3 (NM_144665), HOMER1 (NM_004272), HSPB8 (NM_014365), SOLH (NM_005632), RASGRP1 (NM_005739), LOC124220 (NM_145252), FLJ35880 (NM_153264), CRISPLD476 (NM_153264) CGNL1 (NM_032866), C10orf58 (NM_032333), POF1B (NM_024921), UBR1 (NM_174916), LOC442329 (XM_498220.2), THUMPD1 (NM_017736), KIAA1160 (NM_020701), OLFM4 (NM_H3A12A) (NM_025079), C9orf16 (NM_024112), FLJ13710 (NM_024817), PDZK1IP1 (NM_005764), SEC13L1 (NM_030673), LTBP4 (NM_003573), C20orf129 (NM_030919), CELP (NR_001275), M55NN (MN57M) (NM_130459), PSMD4 (NM_002810), C20orf133 (NM_080676), BENE (NM_005434), GPR172B (NM_017986), C4.4A (NM_014400), EPS8R1 isoform B (NM_017729), MGC15476 (N_0_145056), and TRIB432 (N216) Gene to include

In an embodiment of the present invention, it was confirmed that the expression of these genes in the tissues of patients with exogenous atopic skin diseases, preferably skin tissues, increased or decreased significantly (about 2 times or more) compared to normal samples.

More specifically, at least one expression selected from the group consisting of the following genes is significantly increased in a sample of an exogenous atopic skin disease patient:

POSTN (NM_006475), TNC (NM_002160), VCAM1 (NM_001078), COL1A1 (NM_000088), COL1A2 (NM_000089), COL3A1 (NM_000090), COL12A1 (NM_004370), COL15A1 (NM_001M_X) ECM (extracellular matrix) and cells, including LOXL2 (NM_002318), NOV (NM_002514), MMP2 (NM_004530), MMP12 (NM_002426), DSC1 (NM_004948), CLDN10 (NM_006984), CXADR (NM_001338), COMP (NM_000095) and the like Cell adhesion genes;

Cytokine or chemokine related genes including CCL18 (NM_002988), CXCL14 (NM_004887), CD74 antigen (NM_001025158), and the like;

Antimicrobial peptides and immune response genes including CTSL2 (NM_001333), CTSG (NM_001911), FceRI (NM_002001), CD1E (NM_030893), CD1A antigen (NM_001763), CD200R1 (NM_138806), MNDA (NM_002432), and the like;

Proteolytic enzymes or inhibitors thereof including CPA3 (NM_001870), TPSAB1 (NG_005083), CST6 (NM_001323), CPVL (NM_019029) and the like;

Lipid related genes including THRSP (NM_003251), PLA2G4C (NM_003706), PLA2R1 (NM_001007267), Zn-alpha-2-GP (XM_379897), FADS2 (NM_004265), FABP7 (NM_001446), ANXA2 (NM_001002857), and the like;

MFI2 (NM_005929), RNF152 (NM_173557), RNF24 (NM_007219), SPARC (NM_003118), ZNF90 (M61870), ZNF117 (NM_024498), ZNF185 (NM_007150), SNAI2 (NM_003068), RCN3A (NM_020) (NM_020) Metal binding genes including ADAM9 (NM_001005845) and the like;

Hormone-related genes including MGB1 (NM_002411), PPARG (NM_005037), and the like;

ATP or GTP binding genes including NTRK2 (NM_001007097), NVL (NM_002533), PDK3 (NM_005391), and the like;

Structural genes including LCE2B (NM_014357), KRT18 (NM_000224), CDON (NM_016952), MAPRE2 (NM_014268), and the like;

Heparin binding genes such as UST (NM_005715);

Transcription genes including SOX9 (NM_000346), ID4 (NM_001546), HCLS1 (NM_005335), and the like;

Transport genes including SLC1A2 (NM_004171), SLC16A14 (NM_152527), KDELR3 (NM_006855), RHCG (NM_016321), SOSTDC1 (NM_015464), DARPP-32 (NM_032192), MGST1 (NM_020300), and the like;

Metabolic enzyme genes including ADH1A (NM_000667), ST6GALNAC2 (NM_006456), BBOX1 (NM_003986), PYGL (NM_002863), SOAT1 (NM_003101), and the like;

Nucleic acid binding genes including ZNF664 (NM_152437), ZNF681 (NM_138286), and the like;

Receptor or binding genes including SFRP1 (NM_003012), F2R (NM_001992), FOLR2 (NM_000803) and the like; And

SNX16 (NM_022133), SESN3 (NM_144665), HOMER1 (NM_004272), HSPB8 (NM_014365), SOLH (NM_005632), RASGRP1 (NM_005739), LOC124220 (NM_145252), FLJ35880 (NM_153264), CRISPLD476 (NM_153264) Genes including CGNL1 (NM_032866), C10orf58 (NM_032333), POF1B (NM_024921), UBR1 (NM_174916), LOC442329 (XP_498220), THUMPD1 (NM_017736) and the like.

In addition, expression of one or more selected from the group consisting of the following genes is significantly reduced in samples of patients with exogenous atopic skin diseases.

Extracellular matrix (ECM) and cell adhesion genes, including CEACAM5 (NM_004363), HAS3 (NM_005329), GJB2 (NM_004004), GJB6 (NM_006783), and the like;

Cytokine or chemokine related genes including IL1F9 (NM_019618), IFNA1 (NM_024013), AREG (NM_001657), IL1F6 (NM_014440), and the like;

Antimicrobial peptides and immune response genes including DEFB4 (NM_004942), SERPINB4 (NM_002974), SPINK5 (NM_006846), IFI27 (NM_005532), CD97 (NM_001025160), PI3 (NM_002638), NFKBIZ (NM_001005474) and the like;

TMPRSS11D (NM_004262), KLK4 (NM_004917), KLK6 (NM_001012964), KLK8 (NM_007196), KLK14 (NM_022046), SERPINB12 (NM_080474), SERPINB13 (NM_012397), SERPINB3 (NM_006NM) Proteases or inhibitors thereof including SHH (NM_000193), PRSS3 (NG_001337), USP11 (NM_004651), and the like;

Lipid-related genes including CRABP2 (NM_001878), FABP5 (NM_001444), GM2A (NM_000405), MAL (NM_002371), LDLR (NM_000527), GLTP (NM_016433), and the like;

TCN1 (NM_001062), S100A9 (NM_002965), SLC5A6 (NM_021095), SLC39A2 (NM_014579), TRIM16 (NM_006470), CANT1 (NM_138793), CACNB2 (NM_000724), ARG1 (NM_000045), MYC1, 000, 000, 000, 0000 A metal binding gene comprising a;

Hormone-related genes such as SULT1E1 (NM_005420);

ATP or GTP binding genes including SMMHC (NM_002474), PMCA4 (NM_001001396), GALK2 (NM_001001556), TRPM2 (NM_001001188), Tubulin (alpha 2 isoform 2, NM_079836), RAC1 (NM_006908), PHKG1 (NM_006213) and the like;

Structures including MRPS27 (NM_015084), AMBN (NM_016519), ACTG2 (NM_001615), DES (NM_001927), SSH1 (NM_018984), TAGLN (NM_001001522), LMOD1 (NM_012134), MRPS18A (NM_018135), and RPL10 (NM_006), etc. gene;

Heparin binding genes including PGF (NM_002632), HBEGF (NM_001945), FGFBP1 (NM_005130), and the like;

Transcription genes including FOS (NM_005252), PITX2 (NM_000325), FOSB (NM_006732), MEIS1 (NM_002398), GRHL3 (NM_021180), HSF2BP (NM_007031), MTA2 (NM_004739), and the like;

Transport genes including SLC7A5 (NM_003486), SLC16A10 (NM_018593), and the like;

ARSF (NM_004042), TGM1 (NM_000359), AKR1B10 (NM_020299), CYP2C8 (NM_000770), PGLYRP4 (NM_020393), FUT11 (NM_173540), HADHB (NM_000183), PPP1R12B (NM5283PN) Metabolic enzyme genes including BCKDHA (NM_000709) and the like;

Nucleic acid binding genes including EIF3S9 (NM_003751), MYOCD (NM_153604), HIST4H4 (NM_175054), and the like;

Receptor or binding genes including MUC4 (NM_004532), SEMA6C (NM_030913), KCTD18 (NM_152387), PDLIM7 (NM_005451) and the like; And

KIAA1160 (NM_020701), OLFM4 (NM_006418), CALML1 (GeneID: 809), ZC3H12A (NM_025079), C9orf16 (NM_024112), FLJ13710 (NM_024817), PDZK1IP1 (NM_005764), SEC43063N (M) ), CELP (NR_001275), FAM57B (NM_031478), LPP (NM_005578), TOR2A (NM_130459), PSMD4 (NM_002810), C20orf133 (NM_080676), BENE (NM_005434), GPR172B (NM_017986), C4.41A (N014_N) genes including isoform B (NM_017729), MGC15476 (NM_145056), TRIB2 (NM_021643) and the like.

More preferably, the marker for diagnosing exogenous atopic dermatosis according to one embodiment of the present invention is IFI27 (NM_005532), MAL (NM_002371), BENE (NM_005434), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39 NM_014579), KDELR3 (NM_006855), DEFB4 (NM_004942), SLC16A10 (NM_018593), FAM57B (NM_031478), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-LC-2-A297 (NM_004171), CLDN10 (NM_006984), GJB2 (NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_000405), SOAT1 (NM_003101), HAS3 (NM_005329), and MGST1 (NM_020300) have.

In another embodiment, the present invention provides a marker for diagnosing exogenous atopic skin disease selected from the group consisting of the following SNPs:

SNPs of TNC (NM_002160) including rs13321, rs2274750, rs2104772, rs3748169, rs3748170, rs1061494, rs7020958, rs1061493, rs1757095, rs3827816 and the like;

SNPs of VCAM1 (NM_001078) including rs3783606, rs3170794, rs3170794, rs3783615,34199378, rs34100871, rs3783613, rs3783612, rs3783611, rs34708918, rs34228330 and the like;

SNP of CXADR (NM_001338) such as rs34727960;

SNPs of CEACAM5 (NM_004363) including rs11545767, rs10423171, rs7249230, rs10407503, rs17853315, rs3815780, rs35091611, rs34155934, rs28683503, rs12971352, and the like;

SNPs of COL12A1 (NM_004370) including rs970547, rs34846477, rs34369939, rs35710072, rs35523808, rs34336755, rs34438461, rs240736, rs34730529 and the like;

SNPs of NTRK2 (NM_001007097) including rs1187321, rs2275857, rs1047856 and the like;

SNPs of FceRI (NM_002001) including rs17851282, rs2298805, rs2298804 and the like;

SNPs of CD200R1 (NM_138806) including rs9865242, rs9826308, rs34985808, rs2171509, rs4596117 and the like;

SNPs of KLK4 (NM_004917) including rs2979452, rs34626614, rs2569527, rs1654551 and the like;

SNP of KLK6 (NM_001012964) such as rs11671058;

SNPs of KLK8 (NM_007196) including rs17854057, rs16988799 and the like;

SNPs of KLK14 (NM_022046) including rs7259389, rs7259389, rs35287116, rs2569491, rs2569490 and the like;

SNPs of PLAT (NM_000930) including rs8178872, rs8178674, rs8178672, rs8178672, rs2854290, rs2854290, rs13306819, rs1804182, rs8178747, rs8178748, rs2020921, rs3020630, rs8178733 and the like;

SNPs of CDON (NM_016952) including rs684535, rs12274923, rs35665264, rs3740909, rs7122277, rs3740912 and the like; And

SNPs of ACTG2 (NM_001615) including rs831533, rs3209900, rs3190470 and the like.

In another embodiment, the present invention provides a biochip for diagnosing exogenous atopic dermatosis, which can detect one or more markers for diagnosing exogenous atopic dermatosis, selected from the group consisting of the gene and / or SNP.

More specifically, the biochip for diagnosing exogenous atopic skin disease

Markers for diagnosing exogenous atopic dermatological diseases as described above, preferably IFI27 (NM_005532), MAL (NM_002371), BENE (NM_005434), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC391452 , KDELR3 (NM_006855), DEFB4 (NM_004942), SLC16A10 (NM_018593), FAM57B (NM_031478), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XMM_004197) ), CLDN10 (NM_006984), GJB2 (NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_000405), SOAT1 (NM_003101), HAS3 (NM_005329), and MGST1 (NM_020300). Means that can be measured, such as cDNA for mRNA obtained from the gene, and oligonucleotide probes having sequences complementary to contiguous 5-500 nucleotide sequences in the mRNA;

Means for detecting a protein encoded by the one or more genes, eg, an antibody that reacts with the protein; And

rs13321, rs2274750, rs2104772, rs3748169, rs3748170, rs1061494, rs7020958, rs1061493, rs1757095, rs3827816, rs3783606, rs3170794, rs3170794, rs3783615,34199378, rs34100871, rs3783613, rs3783612, rs3783611, rs34708918, rs34228330, rs34727960, rs11545767, rs10423171, rs7249230, rs10407503, rs17853315, rs3815780, rs35091611, rs34155934, rs28683503, rs12971352, rs970547, rs34846477, rs34369939, rs35710072, rs35523808, rs34336755, rs34438461, rs240736, rs34730529, rs1187321, rs2275857, rs1047856, rs17851282, rs2298805, rs2298804, rs9865242, rs9826308, rs34985808, rs2171509, rs4596117, rs2979452, rs34626614, rs2569527, rs1654551, rs11671058, rs17854057, rs16988799, rs7259389, rs7259389, rs35287116, rs2569491, rs2569490, rs8178872, rs8178674, rs8178672, rs8178672, rs2854290, rs2854290, rs13306819, rs1804182, rs8178747, rs8178748, rs2020921, line in the group consisting of rs3020630, rs8178733, rs684535, rs12274923, rs35665264, rs3740909, rs7122277, rs3740912, rs831533, rs3209900, and rs3190470 Probe for detection of one or more selected SNPs

It may be to include one or more selected from the group consisting of.

Biochip refers to gene expression patterns, gene defects, protein distribution, reaction patterns by combining biological molecules such as polynucleotides (DNA, RNA, etc.) and proteins on small substrates made of glass, silicon, or nylon. Biological Microchip that can be analyzed.

mRNA expression can be measured by RT-PCR, Northern blot, electrophoresis, etc., and protein expression can be measured by enzyme immunoassay (ELISA), fluorescence immunoassay (FIA), radioimmunoassay (RIA), luminescence Immunoassay, immunoblot (immunoblot) method, Western blot (western blot) method, it can be measured by immunostaining method, but is not limited thereto. In addition, the SNP can be detected using a probe known as a detection probe for each SNP, and the probe for each SNP, and a detection method using the same, can be easily understood by those skilled in the art. .

In another embodiment, the present invention provides a method for determining an exogenous atopic skin disease patient using one or more markers for diagnosing exogenous atopic skin disease selected from the group consisting of the gene and / or SNP.

In one embodiment of the invention, the method of determining the exogenous atopic skin disease patients according to the invention

-IFI27 (NM_005532), MAL (NM_002371), BENE (NM_005434), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), KBDLR855 (N_DEF) NM_004942), SLC16A10 (NM_018593), FAM57B (NM_031478), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171) G_DN2 (NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_000405), SOAT1 (NM_003101), HAS3 (NM_005329), and MGST1 (NM_020300) to measure the expression of one or more genes selected from the group consisting of Comparing with the expression level of the gene; And

-Judging the subject as an exogenous atopic skin disease if a change in the expression level of the subject is observed as a result of the comparison.

It may be to include.

More specifically, KDELR3 (NM_006855), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171), CLDN10 (NM_006984), SOAT1 in subjects (NM_003101), and when the expression level of one or more selected from the group consisting of MGST1 (NM_020300) is increased compared to a normal individual, the subject may be determined to be an exogenous atopic skin disease patient. In another embodiment, IFI27 (NM_005532), MAL (NM_002371), BENE (NM_005434), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), DEFB4942 (M_004942) (NM_018593), FAM57B (NM_031478), GJB2 (NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_000405), and HAS3 (NM_005329) when the expression level of at least one selected is reduced compared to normal subjects The specimen may be considered to be an exogenous atopic skin disease.

In another example, the method of determining the exogenous atopic skin disease patients according to the present invention

-Rs13321, rs2274750, rs2104772, rs3748169, rs3748170, rs1061494, rs7020958, rs1061493, rs1757095, rs3827816, rs3783606, rs3170794, rs3170794, rs3783615,34199313 , rs11545767, rs10423171, rs7249230, rs10407503, rs17853315, rs3815780, rs35091611, rs34155934, rs28683503, rs12971352, rs970547, rs34846477, rs34369939, rs35710072, rs35523808, rs34336755, rs34438461, rs240736, rs34730529, rs1187321, rs2275857, rs1047856, rs17851282, rs2298805, rs2298804 , rs9865242, rs9826308, rs34985808, rs2171509, rs4596117, rs2979452, rs34626614, rs2569527, rs1654551, rs11671058, rs17854057, rs16988799, rs7259389, rs7259389, rs35287116, rs2569491, rs2569490, rs8178872, rs8178674, rs8178672, rs8178672, rs2854290, rs2854290, rs13306819, rs1804182 , rs8178747, rs8178748, rs2020921, rs3020630, rs8178733, rs684535, rs12274923, rs35665264, rs3740909, rs7122277, rs3740912, rs831533, rs3209900, Measuring a 1 SNP exists more member selected from the group consisting of rs3190470; And

Judging the subject as an exogenous atopic skin disease if the SNP is present in the subject's sample.

It may be to include.

In another example, the present invention provides a method for searching for an exogenous atopic dermatosis trigger by using one or more markers for diagnosing exogenous atopic dermatitis, selected from the group consisting of the gene and / or SNP.

According to one embodiment of the present invention, a method for searching for an exogenous atopic dermatitis inducer is

Contacting the candidate with a biopsy sample;

IFI27 (NM_005532), MAL (NM_002371), BENE (NM_005434), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), KDELR855 (NM_DEF) NM_004942), SLC16A10 (NM_018593), FAM57B (NM_031478), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171) G_DN2 Measuring the expression level of at least one gene selected from the group consisting of (NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_000405), SOAT1 (NM_003101), HAS3 (NM_005329), and MGST1 (NM_020300);

Comparing the expression level measured in the sample contacted with the candidate with the expression level of the gene in the sample not contacted with the candidate; And

As a result of the comparison, KDELR3 (NM_006855), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171), CLDN10 (NM_006984) , At least one expression level selected from the group consisting of SOAT1 (NM_003101), and MGST1 (NM_020300) is increased compared to normal individuals, or IFI27 (NM_005532), MAL (NM_002371), BENE (NM_005434), GPR172B (NM_017986 ), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), DEFB4 (NM_004942), SLC16A10 (NM_018593), FAM57B (NM_031478), GJB2 (NM_004004), PDZK1IPN (NM_004004), NZ_A005N NM_005329) when the expression level of one or more selected from the group consisting of reduced in comparison with the normal subject, judging the candidate substance as a cause of exogenous atopic skin disease

It may be to include.

In another embodiment, the present invention provides a method for searching for a prophylactic or therapeutic substance for exogenous atopic dermatitis using at least one marker for diagnosing exogenous atopic dermatitis, selected from the group consisting of the gene and / or SNP. .

A method for preventing, alleviating, and / or treating a substance for exogenous atopic dermatitis according to one embodiment of the present invention is

Contacting the candidate with a sample obtained from an exogenous atopic skin disease patient;

IFI27 (NM_005532), MAL (NM_002371), BENE (NM_005434), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), KDELR855 (NM_DEF) NM_004942), SLC16A10 (NM_018593), FAM57B (NM_031478), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171) G_DN2 Measuring at least one expression level selected from the group consisting of (NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_000405), SOAT1 (NM_003101), HAS3 (NM_005329), and MGST1 (NM_020300);

Comparing the expression level measured in the sample of the atopic skin disease patient contacted with the candidate with the expression level of the corresponding gene in the sample of the atopic skin disease patient not contacted with the candidate; And

As a result of the comparison, KDELR3 (NM_006855), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171), CLDN10 (NM_006984) , The level of expression of one or more selected from the group consisting of SOAT1 (NM_003101), and MGST1 (NM_020300) is less than the expression level of the gene in the sample without contact with the candidate, or IFI27 (in the sample contacted with the candidate). NM_005532), MAL (NM_002371), BENE (NM_005434), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), DEFB4 (NM_004942), SAM167893J NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_000405), and HAS3 (NM_005329) when the level of expression of one or more selected from the group of the candidate substance is not increased than the expression level of the corresponding gene in the non-contact sample, Prevent, reduce and / or exogenous atopic dermatitis The step of determining a treatment material

It may be to include.

The subject, exogenous atopic dermatitis patient and normal subject herein can be any animal, preferably a mammal, more preferably a human, and the sample or biopsy sample obtained therefrom can be any tissue, bodily fluid, or cell. For example skin tissue or skin cells or fibroblasts. In addition, a normal individual refers to an individual who does not have symptoms and signs of atopic dermatological diseases and who does not have a history of atopic diseases in an individual and family. In addition, in the present specification, atopic dermatitis refers to atopic dermatitis in a narrow sense, and broadly used to mean atopic dermatitis, including atopic dermatitis, which is not accompanied by inflammation.

In the present invention, it is possible to identify the cause genes involved in exogenous atopic dermatitis, and to select the target genes for the treatment, so that it is expected to be used not only for the development of various therapeutic agents but also for the determination of the effects of the conventionally developed therapeutic agents. It is possible to identify individual differences in individual patients and provide a basis for the genes of evidence for personalized medicine.

Hereinafter, the present invention will be described in more detail with reference to the following examples. The following examples are only for illustrating the present invention, but the scope of the present invention is not limited by these examples.

Example  1. Atopic Dermatitis Sample Preparation

From non-asthmatic atopic patients were taking exogenous atopic dermatitis lesions skin samples (Park YD, including: Towards a proteomic analysis of atopic dermatitis : a two-dimensional-polyacrylamide gel electrophoresis / mass spectrometric analysis of cultured patient-derived fibroblasts Proteomics 4.: 3446 3455, 2004, and CW Jeong including:. Differential in vivo cytokine mRNA expression in lesional skin of atopic dermatitis patients intrinsic vs. extrinsic using semiquantitative RT-PCR Clin Exp Allergy 33: 1717 1724, 2003). Plastic surgery was used to obtain skin samples from normal control subjects ( n = 10) with no atopic symptoms and no personal and family history of atopic disease. A 5 mm diameter punch biopsy was taken from the lesion skin of an exogenous atopic dermatitis patient (all males, n = 30). The total IgE level, eosinophil count, SCORAD (SCORing Atopic Dermatitis), and age mean of each group of exogenous atopic dermatitis patients were 1739 U / mL, 625 / μL, 43.84 and 21.1 years, respectively. Experimental consent was obtained for both individual patient and normal controls. This example was carried out in accordance with the Declaration of Helsinki and proceeded with the written consent of all participants.

Example  2. Microarray  making

Total RNA isolation, labeling and hybridization is described by Kim T et al .: Downregulation of lipopolysaccharide response in Drosophila by negative crosstalk between the AP1 and NF-kappaB signaling modules. Nat Immunol 6 : 211 218, 200 'and' Park YD et al .: Towards profiling the gene expression of fibroblasts from atopic dermatitis patients: human 8K complementary DNA microarray. Clin Exp Allergy 36 : 649 657, 2006 '. That is, total RNA was isolated from skin tissue samples obtained from each subject (one RNA per patient). The concentrations of the 10 normal RNA samples and 10 exogenous atopic dermatitis RNA samples thus separated were measured and mixed at the same concentration. Correspondingly pooling resulted in normal pooling samples and exogenous atopic dermatitis pooling samples, respectively. CDNA template was prepared for each pooled sample and labeled with Cy3 dye and Cy5 dye. GenePlorer ^™ Human-34K chip (Digital) in the presence of hybridization solution (25% formamide, 5 x SSC, 0.1% SDS, 25 μg / ml Cot-1 DNA, 10% dextran sulfate, etc., Digital Genomics) for 16 hours at 42 ° C Genomics, Seoul, Korea) were hybridized with a mixture of fluorescently labeled cDNAs obtained from normal control and atopic dermatitis patient samples.

Each slide was scanned with Scanarray Lite (PerkinElmer Life Science, Billerica, Mass.). Gene expression rates were determined by image analysis using GenePix Pro 3.0 (Axon Instruments, Union City, CA). Gene expression log values were normalized by LOWESS regression. The regression analysis was performed for each exogenous atopic dermatitis pooling sample (Groups 1, 2 and 3) vs normal pooling sample, and exogenous atopic dermatitis pooling sample (Group 1) vs exogenous atopic dermatitis pooling sample Group 2, respectively. . As a result, three slides were made to profile differently regulated genes in exogenous atopic dermatitis, and one slide was made to measure patient-to-patient variation. In order to minimize deviations between patients and to enhance the certainty of the results obtained from the few samples used in this example, up- and down-regulated genes (which show a sensitization when compared to two or more control groups) are normal. Candidate genes selected by excluding the exogenous atopic dermatitis-exogenous atopic dermatitis slide results from the three exogenous atopic dermatitis-normal control slides for comparison between groups and exogenous atopic patient groups as well as for comparative deviations between exogenous patient groups. In other words, the results obtained on the slide consisting of the normal group and the exogenous group were different from the results obtained on the slides of the exogenous groups.

Example  3. RT- PCR

Total RNA was extracted from four groups of exogenous atopic dermatitis patients and four normal controls (skin tissue taken plastically). Primer sequences for the target genes were designed using the Primer 3 program ( http://frodo.wi.mit.edu/ ) based on GENBANK listed sequences, and the sequences are shown in Table 1 below.

TABLE 1 Primers used for RT-PCR

primer order Bp expected Fc fragment of IgE high affinity I receptor (FceRI) Forward 5'-TGTGGCAGCTGGACTATGAG-3 '(SEQ ID NO: 1) 291 Reverse 5'-CAATTGCTGATGCTGGAAAA-3 '(SEQ ID NO: 2) Fatty acid binding protein 7, brain (FABP7) Forward 5'-CCAGCTGGGAGAAGAGTTTG-3 '(SEQ ID NO: 3) 196 Reverse 5'-CTCATAGTGGCGAACAGCAA-3 '(SEQ ID NO: 4) Carboxypeptidase A3 (CPA3) Forward 5'-ACTTGGCCAAAACCAATGAG-3 '(SEQ ID NO: 5) 261 Reverse 5'-TCCAAGCCACAATCTTTTCC-3 '(SEQ ID NO: 6) Arylsulfatase F (ARSF) Forward 5'-GGACGACAGTGGGTCAGTTT-3 '(SEQ ID NO: 7) 179 Reverse 5'-GTGTCAGGGGTGTGGACTCT-3 '(SEQ ID NO: 8) Amphiregulin
(AREG) Forward 5'-AAGCGTGAACCATTTTCTGG-3 '(SEQ ID NO: 9) 296 Reverse 5'-CCATTTTTGCCTCCCTTTTT-3 '(SEQ ID NO: 10) Gap junction protein, beta 2 (GJB2) Forward 5'-ACTCCACCAGCATTGGAAAG-3 '(SEQ ID NO: 11) 172 Reverse 5'-TGGGAGATGGGGAAGTAGTG-3 '(SEQ ID NO: 12) Glycolipid transfer protein (GLTP) Forward 5'-TCCTGGAGGTGGAGAAAGAA-3 '(SEQ ID NO: 13) 297 Reverse 5'-TAACATTCTGCCCCTTGGAG-3 '(SEQ ID NO: 14) Hyaluronan synthase 3 (HAS3) Forward 5'-GTCAGTGGTCACGGGTTTCT-3 '(SEQ ID NO: 15) 297 Reverse 5'-AGGCCAATGAAGTTCACCAC-3 '(SEQ ID NO: 16) Histone 4, H4 (HIST4H4) Forward 5'-AAGCGCATTTCTGGTCTCAT-3 '(SEQ ID NO: 17) 220 Reverse 5'-AAGGGCCTTTTGGAGTCTGT-3 '(SEQ ID NO: 18)

PCR was carried out under the following conditions: 1) performing an initial denaturation step for all samples for 2 minutes at 94 ° C., 2) performing a denaturation step for 30 seconds at 94 ° C., performing an annealing step for 20 seconds at 60 ° C., and 60 seconds at 72 ° C. Extension step, 30 repetitions, 3) then final extension step at 72 ° C. for 5 minutes.

Example 4. PSIMAP  And PEIMAP  algorithm

Prediction of protein-protein interactions (PPI) in this example was performed using most of the currently available major forms of PPI algorithms. PPI algorithms used include the following: 1) Protein Structural Interactome MAP (PSIMAP, http://psimap.com )-Method of using protein structural domains of the Structural Classification of Proteins (SCOP) database [Murzin AG et al .: SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol 247 : 536 540, 1995; And 2) Protein Experimental Interactome MAP (PEIMAP) —a conventional method using public resources of experimental protein interaction information such as HPRD, BIND, DIP, MINT, IntAct and BioGrid.

The basic process of PSIMAP is to infer interactions between proteins using nearby homologs. Predictions are based on interactions between domains or proteins on known Protein Data Bank (PDB) structures. If an unknown protein has a homologue for a domain of known structure, PSIMAP assumes that the unknown protein interacts with its homologous partner. This concept is called 'homologous interaction'.

The unique interaction between two proteins or two domains is based on the Euclidean distance, ie whether the two domains are in physical contact with each other. Thus, PSIMAP provides interactive prediction based on three-dimensional structure. PEIMAP consists of a combination of several of the aforementioned experimental protein-protein interaction databases. Redundancy checks were performed to remove identical protein sequences from the interaction database. Currently, 116,773 protein and 229,799 interactions are included. By combining PSIMAP and PEIMAP, one can obtain broad and reliable PPI predictions for possible new gene targets. When expression data such as microarrays are enriched, PPI predictive interaction partners will be able to provide new information on gene regulatory pathways associated with disease.

[Result analysis]

1. Human 34K- Oligo Chip Microarrays  SAM (significance analysis of microarray) analysis

'Park YD et al .: Towards profiling the gene expression of fibroblasts from atopic dermatitis patients: human 8K complementary DNA microarray. Clin A SAM (significance analysis of microarray) analysis was performed as described in Exp Allergy 36 : 649 657, 2006 '. Genes showing significant expression changes (> 2-fold) were selected using a 5% cut-off of q value.

SAM analysis revealed 228 candidate genes, 97 of which were upregulated in exogenous atopic dermatitis patients compared to normal controls, and 131 genes were downregulated in exogenous atopic dermatitis patients compared to normal controls. It became. The results are shown in FIG. 1 and Table 2.

1 shows cDNA microarray results of biopsy tissue from exogenous atopic dermatitis patients: (a) is pooling patient group 1 vs pooling normal group; (b) pooling patient group 2 vs pooling normal group; (c) pooling patient group 3 vs pooling normal group; And (d) pooling patient group 1 vs pooling patient group 2. The analysis was performed using a GenePlorer ^™ Human-34K chip (Digital Genomics, Seoul, Korea). In order to minimize intervariability among patients, candidate genes selected from (a) to (c) were reconfirmed by excluding results of (d), and candidate genes that were upregulated more than two times or downregulated more than two times were considered false positive It was.

TABLE 2 Genes up- or down-regulated more than two-fold in exogenous atopic dermatitis patients compared to normal controls

Gene name Accession no Intensity q value (%) Functions A. ECM and cell adhesion related genes Periostin (POSTN; osteoblast specific factor 2; fasciclin I-like) NM_006475 5.01 0.63 heparin binding; ECM component Tenascin C (TNC; Hexabrachion) NM_002160 2.85 0.63 cell adhesion; protein binding; ECM component Vascular cell adhesion protein 1 (VCAM1) ^a NM_001078 2.67 / 1.93 0.63 / 2.45 cell-cell adhesion; protein binding Collagen type I, alpha 1 chain precursor (COL1A1) ^a NM_000088 2.10 / 1.95 / 1.86 2.02 / 4.65 / 4.65 ECM structural constituent Collagen type I, alpha 2 chain (COL1A2) NM_000089 1.82 0.63 ECM structural constituent Collagen, type III, alpha 1 (COL3A1) NM_000090 2.57 4.65 ECM structural constituent Collagen type XII, alpha 1 chain precursor (COL12A1) NM_004370 2.06 0.63 cell adhesion; ECM component Collagen type XV, alpha 1 chain precursor (COL15A1) ^a NM_001855 2.04 / 1.80 2.45 / 0.63 cell adhesion; ECM component Cadherin 11, type 2, osteoblast (CDH11) NM_001797 1.84 2.02 calcium ion binding; cell adhesion Lysyl oxidase (EC 1.4.3.13) (LOX) NM_002317 2.14 0.63 copper ion binding; ECM formation Lysyl oxidase-like 2 precursor (LOXL2) NM_002318 2.07 0.63 copper ion binding; cell adhesion Nephroblastoma overexpressed gene (NOV) NM_002514 1.62 0.63 growth factor activity; ECM component Matrix metalloproteinase 2 (EC 3.4.24.24) (MMP2) NM_004530 1.52 0.63 calcium / zinc binding; ECM component; gelatinase A activity Matrix metalloproteinase 12 (macrophage elastase) (EC 3.4.24.65) (MMP12) NM_002426 1.36 4.65 calcium / zinc ion binding; ECM breakdown Desmocollin 1 (DSC1) NM_004948 1.88 0.63 calcium ion binding; cell adhesion Claudin 10 (CLDN10) NM_006984 1.88 0.63 structural molecule activity; cell adhesion Coxsackievirus and adenovirus receptor (CXADR) ^a NM_001338 1.62 / 1.58 / 1.57 / 1.42 0.63 / 0.63 / 0.63 / 0.63 protein binding; receptor activity; cell adhesion  Cartilage oligomeric matrix protein (COMP) NM_000095 1.49 0.63 calcium ion binding; ECM structural constituent Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) NM_004363 -2.63 2.02 cell adhesion Hyaluronan synthase 3 (EC 2.4.1.212) (HAS3) NM_005329 -2.01 0.63 hyaluronan synthase activity; transferase activity Gap junction protein, beta 2, 26kDa (connexin 26; GJB2) NM_004004 -2.38 0.63 connexon channel activity Gap junction protein, beta 6 (connexin 30) (GJB6) NM_006783 -1.63 0.63 connexon channel activity B. Cytokines Of chemokines  and their associated genes Chemokine (C-C motif) ligand 18 (CCL18) NM_002988 3.58 0.63 chemokine activity Chemokine (C-X-C motif) ligand 14 (CXCL14) NM_004887 1.77 2.02 chemokine activity MHC HLA-DR gamma chain (CD74 antigen) NM_001025158 1.47 2.02 MHC class II receptor activity; cytokine binding Interleukin 1 family, member 9 (IL1F9) NM_019618 -2.61 0.63 interleukin-1 receptor antagonist activity; immune response Interferon, alpha 1 (IFNA1) NM_024013 -2.04 2.45 signaling pathway; cytokine activity Amphiregulin (AREG) NM_001657 -1.97 4.65 cytokine activity; growth factor activity Interleukin 1 family, member 6 (epsilon) (IL1F6) NM_014440 -1.44 4.65 interleukin-1 receptor binding; inflammatory response C. Antimicrobial peptides and immune response genes Cathepsin L2 precursor (EC 3.4.22.43) (CTSL2) NM_001333 2.06 0.63 cathepsin L activity Cathepsin G (EC 3.4.21.20) (CTSG) NM_001911 1.12 4.01 cathepsin G activity; peptidase activity; immune response Defensin, beta 4 (DEFB4) ^a NM_004942 -1.86 / -1.78 0.63 / 2.45 antibiotic peptide; immune response  High affinity immunoglobulin epsilon receptor alpha-subunit precursor (FceRI) NM_002001 2.51 0.63 IgE binding; receptor activity CD1E antigen (CD1E) ^a NM_030893 2.66 / 2.23 0.63 / 0.63 immune response T-cell surface glycoprotein CD1A precursor (CD1A antigen) NM_001763 1.73 2.45 immune response; MHC class I receptor activity CD200 receptor 1 (CD200R1) NM_138806 2.65 0.63 receptor activity Myeloid cell nuclear differentiation antigen (MNDA) NM_002432 1.42 4.65 DNA binding; cellular defense response Serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 4 (SERPINB4) NM_002974 -2.47 0.63 serine-type endopeptidase inhibitor activity; immune response Serine protease inhibitor, Kazal type 5 (SPINK5) NM_006846 -2.31 0.63 serine-type endopeptidase inhibitor activity; anti-inflammatory response Interferon, alpha-inducible protein 27 (IFI27) NM_005532 -1.56 4.01 immune response CD97 antigen (CD97) NM_001025160 -1.48 / -1.29 2.02 / 4.65 inflammatory response; G-protein coupled receptor activity; calcium ion binding Protease inhibitor 3, skin-derived; elafin precursor (PI3) NM_002638 -4.20 0.63 protein binding; LPS detoxification; anti-inflammatory role; ECM Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta (NFKBIZ) NM_001005474 -1.23 2.45 inflammatory responses to LPS; an activator of IL-6 production D. Proteolytic  enzymes and their inhibitors Carboxypeptidase A3 (mast cell) precursor (CPA3) NM_001870 2.41 0.63 carboxypeptidase A activity Tryptase alpha / beta 1 (EC 3.4.21.59) (TPSAB1) ^a NG_005083 2.33 / 2.23 0.63 / 0.63 chymotrypsin activity; tryptase activity Cystatin E / M (CST6) NM_001323 2.19 4.65 cysteine protease inhibitor activity Serine carboxypeptidase vitellogenic-like (CPVL) NM_019029 2.08 4.65 peptidase activity  Airway trypsin-like protease (TMPRSS11D) NM_004262 -3.83 0.63 chymotrypsin / peptidase activity; ECM Kallikrein 4 (prostase, enamel matrix, prostate) (KLK4) NM_004917 -1.46 0.63 chymotrypsin / trypsin activity; Kallikrein 6 (KLK6) NM_001012964 -1.85 2.45 chymotrypsin / peptidase activity Kallikrein 8 (neuropsin / ovasin) (KLK8) NM_007196 -2.06 0.63 chymotrypsin / trypsin activity Kallikrein 14 (KLK14) NM_022046 -3.60 0.63 chymotrypsin / peptidase activity; ECM Serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 12 (SERPINB12) NM_080474 -3.02 0.63 enzyme binding; trypsin inhibitor activity Hurpin (SERPINB13) NM_012397 -2.04 2.02 serine-type endopeptidase inhibitor activity; response to UV Serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3 (SERPINB3) NM_006919 -1.94 4.01 serine-type endopeptidase inhibitor activity Tissue-type plasminogen activator (PLAT) NM_000930 -2.08 0.63 plasminogen activator activity; chymotrypsin / peptidase activity Cystatin A (CSTA) NM_005213 -1.54 4.65 cysteine protease inhibitor activity Sonic hedgehog homolog (Drosophila) (SHH) NM_000193 -1.33 2.02 peptidase activity Protease, serine, 3 (mesotrypsin) (PRSS3) NG_001337 -1.40 4.01 calcium ion binding; chymotrypsin activity Ubiquitin specific peptidase 11 (USP11) NM_004651 -1.44 4.65 cysteine-type endopeptidase activity; ubiquitin thiolesterase activity E. Lipid-associated genes Thyroid hormone-inducible hepatic protein (THRSP) NM_003251 3.33 0.63 lipid metabolism  Phospholipase A2 (EC 3.1.1.4) (PLA2G4C) NM_003706 3.04 0.63 calcium ion binding; lipid catabolism Phospholipase A2 receptor 1, 180 kDa (PLA2R1) NM_001007267 1.34 2.45 receptor activity Similar to Zinc-alpha-2-glycoprotein precursor (Zn-alpha-2-GP) XM_379897 2.58 0.63 fatty acid binding; a lipid mobilizing factor Fatty acid desaturase 2 (FADS2) NM_004265 2.70 0.63 20- and 22-carbon polyenoic fatty acids synthesis Fatty acid-binding protein 7, brain (FABP7) NM_001446 2.57 0.63 lipid binding Annexin A2 (ANXA2) NM_001002857 1.16 4.65 calcium ion / skeletal protein binding; phospholipase inhibitor activity Cellular retinoic acid binding protein 2 (CRABP2) NM_001878 -2.05 0.63 lipid / retinal binding Fatty acid-binding protein 5 (FABP5) ^a NM_001444 -1.82 / -1.56 2.02 / 4.01 fatty acid binding GM2 ganglioside activator (GM2A) NM_000405 -1.63 2.45 sphingolipid activator protein activity Mal, T-cell differentiation protein (MAL) NM_002371 -1.05 4.65 channel / pore class transporter activity; apoptotic protease activator activity; lipid binding Low-density lipoprotein receptor (LDLR) NM_000527 -1.45 0.63 calcium ion binding; lipid transporter activity Glycolipid transfer protein (GLTP) NM_016433 -1.43 2.45 intermembrane transfer of glycolipids F. Metal binding genes Melanoma-associated antigen P97 (MFI2) NM_005929 2.72 0.63 ferric iron binding Ring finger protein 152 (RNF152) NM_173557 1.79 2.02 metal ion binding; protein ubiquitination Ring finger protein 24 (RNF24) NM_007219 1.53 0.63 metal binding; protein ubiquitination Secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) NM_003118 1.65 2.45 calcium / copper ion / collagen binding  Zinc finger protein 90 (HTF9) (ZNF90) M61870 1.62 2.45 metal ion binding; transcription factor activity Zinc finger protein 117 (HPF9) (ZNF117) NM_024498 1.31 0.63 nucleic acid / metal binding; transcription activity Zinc finger protein 185 (LIM-domain) (ZNF185) NM_007150 -1.48 0.63 zinc ion binding Neural crest transcription factor SLUG (SNAI2) NM_003068 1.42 4.65 DNA binding; metal ion binding Reticulocalbin 3, EF-hand calcium binding domain (RCN3) NM_020650 1.29 4.65 calcium ion binding Serine / threonine protein phosphatase 2A, 72/130 kDa regulatory subunit B (PPP2R3A) NM_002718 1.26 2.02 calcium ion binding; hydrolase / phosphatase activity A disintegrin and metalloproteinase domain 9 (meltrin gamma) (ADAM9) NM_001005845 1.23 4.01 SH3 domain / metal ion / integrin binding; metalloproteinase activity Transcobalamin I (TCN1) NM_001062 -2.55 0.63 cobalt ion transporter activity S100 calcium binding protein A9 (calgranulin B) (S100A9) NM_002965 -2.42 2.45 calcium ion binding; signal transducer activity Solute carrier family 5 (sodium-dependent vitamin transporter), member 6 (SLC5A6) NM_021095 -2.20 0.63 sodium ion binding; transporter activity Solute carrier family 39 (zinc transporter), member 2 (SLC39A2) NM_014579 -1.66 0.63 metal ion transporter activity Tripartite motif-containing 16 (TRIM16) NM_006470 -1.49 4.65 metal ion binding; transcription factor activity Calcium activated nucleotidase 1 (CANT1) NM_138793 -1.49 2.45 signal transducer activity; calcium ion binding Calcium channel, voltage-dependent, beta 2 subunit (CACNB2) NM_000724 -1.48 2.02 voltage-gated calcium channel activity; calcium ion binding Arginase, liver (EC 3.5.3.1) (ARG1) NM_000045 -1.13 4.65 arginase / hydrolase activity; metal ion binding  Myelin transcription factor 1 (MYT1) NM_004535 -1.11 4.65 transcription factor activity; metal ion binding Small proline-rich protein 2C (SPRR2C) NG_005086 -2.29 0.63 metal ion binding G. Hormone related genes Mammaglobin 1 (MGB1; SCGB2A2) NM_002411 6.07 0.63 steroid binding Peroxisome proliferative activated receptor, gamma (PPARG) ^a NM_005037 2.56 / 2.46 0.63 / 0.63 metal ion binding; protein binding; steroid hormone receptor activity Sulfotransferase family 1E, estrogen-preferring, member 1
(SULT1E1) NM_005420 -2.93 2.02 estrone sulfotransferase activity; steroid binding H. ATP / GTP  binding genes BDNF / NT-3 growth factors receptor precursor (EC 2.7.1.112) (NTRK2) NM_001007097 1.69 0.63 ATP / neurotrophin / nucleotide binding; transmembrane receptor protein tyrosine kinase activity Nuclear VCP-like (NVL) NM_002533 1.49 0.63 ATP binding Pyruvate dehydrogenase kinase isoform 3 (PDK3) ^a NM_005391 1.43 / 1.30 2.02 / 4.01 ATP binding; protein kinase activity Myosin heavy chain, smooth muscle isoform (SMMHC; MYH11) NM_002474 -2.04 2.45 ATP / actin / calmodulin binding; motor activity Plasma membrane calcium-transporting ATPase 4 (EC 3.6.3.8) (PMCA4; ATP2B4) NM_001001396 -1.98 0.63 ATP / actin / calmodulin binding; hydrolase activity Galactokinase 2 (GALK2) NM_001001556 -1.83 2.45 galactokinase activity; ATP binding Transient receptor potential cation channel, subfamily M, member 2 (TRPM2) NM_001001188 -1.61 4.01 ADP-ribose diphosphatase activity; calcium channel activity; hydrolase activity Tubulin, alpha 2 isoform 2 NM_079836 -1.60 0.63 GTP binding  DEAD (Asp-Glu-Ala-Asp) box polypeptide 27 (DDX27) NM_017895 -1.55 4.01 ATP binding; ATP-dependent helicase activity; hydrolase activity Ras-related C3 botulinum toxin substrate 1 (RAC1) NM_006908 -1.51 2.45 GTP binding Phosphorylase kinase, gamma 1 (muscle) (EC 2.7.1.38) (PHKG1) NM_006213 -1.19 4.01 ATP binding; phosphorylase kinase activity I. Structural genes Late cornified envelope 2B (LCE2B) NM_014357 2.39 0.63 epidermis development Keratin, type I cytoskeletal 18 (KRT18) NM_000224 1.71 4.65 structural constituent of cytoskeleton Surface glycoprotein, Ig superfamily member (CDON) NM_016952 1.40 4.01 myogenic differentiation Microtubule-associated protein, RP / EB family, member 2 (MAPRE2) NM_014268 1.04 4.65 microtubule binding; cell cycle / division Mitochondrial ribosomal protein S27 (MRPS27) NM_015084 -1.43 4.01 structural constituent of ribosome Ameloblastin, enamel matrix protein (AMBN) NM_016519 -2.39 0.63 structural constituent of tooth enamel Actin, gamma 2, smooth muscle, enteric (ACTG2) NM_001615 -2.22 4.01 motor activity; ATP binding; structural constituent of cytoskeleton Desmin (DES) NM_001927 -2.33 0.63 structural constituent of cytoskeleton Slingshot 1 (SSH1) NM_018984 -1.93 0.63 regulation of actin cytoskeleton Transgelin (TAGLN) NM_001001522 -1.83 2.02 actin binding Leiomodin 1 (LMOD1) ^a NM_012134 -1.78 / -1.66 0.63 / 4.01 tropomyosin binding Mitochondrial ribosomal protein S18A (MRPS18A) NM_018135 -1.31 2.45 structural constituent of ribosome Ribosomal protein L10 (RPL10) NM_006013 -1.22 4.01 structural constituent of ribosome J. Heparin binding genes Uronyl-2-sulfotransferase (UST) NM_005715 1.22 4.65 chondroitin / heparan sulfate biosynthesis  Placental growth factor, vascular endothelial growth factor-related protein (PGF) NM_002632 -1.54 4.01 growth factor activity; heparin binding Heparin-binding EGF-like growth factor (HBEGF) NM_001945 -1.25 4..01 epidermal growth factor receptor binding; heparin binding Fibroblast growth factor binding protein 1 (FGFBP1) NM_005130 -1.75 2.02 heparin binding K. Transcriptional genes Transcription factor SOX9 (SOX9) NM_000346 1.59 2.02 DNA binding; specific RNA polymerase (II) activity Inhibitor of DNA binding 4, dominant negative helix-loop-helix protein (ID4) NM_001546 1.42 2.02 transcription regulator activity Hematopoietic cell-specific LYN substrate 1 (HCLS1) NM_005335 1.32 2.02 transcription factor activity Cellular oncogene fos (FOS) NM_005252 -3.06 0.63 DNA binding; specific RNA polymerase II transcription factor activity Paired-like homeodomain transcription factor 2 (PITX2) ^a NM_000325 -2.91 / -1.30 0.63 / 4.65 transcription factor activity FBJ murine osteosarcoma viral oncogene homolog B (FOSB) NM_006732 -2.47 0.63 DNA binding; transcription factor binding; cell cycle Meis1, myeloid ecotropic viral integration site 1 homolog (MEIS1) NM_002398 -2.16 2.45 transcription factor activity Sister-of-mammalian grainyhead (GRHL3) NM_021180 -1.90 0.63 transcription factor Heat shock transcription factor 2 binding protein (HSF2BP) NM_007031 -1.78 0.63 HSF2 activation Metastasis associated 1 family, member 2 (MTA2) NM_004739 -1.34 2.45 transcription factor activity; metal ion binding L. Transporter genes Solute carrier family 12 member 2 (SLC1A2) NM_004171 3.80 0.63 L-glutamate / polyamine transporter activity Solute carrier family 16 (monocarboxylic acid transporters), member 14 (SLC16A14) NM_152527 2.01 0.63 transporter activity  ER lumen protein retaining receptor 3 (KDELR3) NM_006855 1.32 2.45 protein transporter activity Rhesus blood group, C glycoprotein (RHCG) NM_016321 -4.95 0.63 ammonium transporter activity Sclerostin domain containing 1 (SOSTDC1) NM_015464 3.18 0.63 bone morphogenetic protein antagonist Dopamine and cAMP-regulated phosphoprotein (DARPP-32) NM_032192 3.13 0.63 protein kinase inhibitor activity Microsomal glutathione S-transferase 1 (EC 2.5.1.18) (MGST1) NM_020300 2.62 0.63 glutathione transferase activity Large neutral amino acids transporter small subunit 1 (SLC7A5) NM_003486 -1.67 2.02 amino acid permease activity; neutral amino acid transporter activity Solute carrier family 16 (monocarboxylic acid transporters), member 10 (SLC16A10) NM_018593 -1.64 2.45 transporter activity M. Metabolic enzymes Alcohol dehydrogenase alpha chain (EC 1.1.1.1) (ADH1A) NM_000667 2.16 4.01 alcohol dehydrogenase activity ST6 (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl-1,3) -N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2) NM_006456 1.50 0.63 sialyltransferase activity Butyrobetaine (gamma), 2-oxoglutarate dioxygenase (gamma-butyrobetaine hydroxylase) 1 (BBOX1) NM_003986 1.47 4.01 gamma-butyrobetaine dioxygenase activity; iron ion binding Glycogen phosphorylase, liver form (EC 2.4.1.1) (PYGL) NM_002863 1.45 4.01 glycogen phosphorylase activity Sterol O-acyltransferase 1 (EC 2.3.1.26) (SOAT1) NM_003101 1.37 4.65 acyltransferase / sterol O-acyltransferase activity Arylsulfatase F (ARSF) NM_004042 -2.95 4.01 arylsulfatase activity; calcium ion binding Transglutaminase 1 (TGM1) NM_000359 -2.47 0.63 acyltransferase activity; calcium ion binding  Aldo-keto reductase family 1, member B10 (aldose reductase) (AKR1B10) NM_020299 -2.16 4.01 aldo-keto / aldehyde reductase activity cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) NM_000770 -2.09 0.63 monooxygenase activity; metal ion binding Peptidoglycan recognition protein 4 (PGLYRP4) NM_020393 -1.95 2.02 peptidoglycan receptor activity; N-acetylmuramoyl-L-alanine amidase activity Fucosyltransferase 11 (alpha (1,3) fucosyltransferase) (FUT11) NM_173540 -1.82 0.63 fucosyltransferase activity 3-Ketoacyl-Coenzyme A thiolase (EC 2.3.1.16) (HADHB) NM_000183 -1.62 2.45 3-hydroxyacyl-CoA dehydrogenase activity Protein phosphatase 1, regulatory (inhibitor) subunit 12B (PPP1R12B) NM_002481 -1.62 0.63 enzyme activator activity Stratifin (SFN) NM_006142 -1.58 2.45 protein domain specific binding; protein kinase C inhibitor activity Peptidoglycan recognition protein 3 (PGLYRP3) NM_052891 -1.46 4.65 N-acetylmuramoyl-L-alanine amidase activity; peptidoglycan receptor activity Branched chain keto acid dehydrogenase E1, alpha polypeptide (EC 1.2.4.4) (BCKDHA) NM_000709 -1.24 4.01 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity N. Nucleic acid binding Zinc finger protein 664 (ZNF664) NM_152437 1.21 4.01 nucleic acid binding Zinc finger protein 681 (ZNF681) NM_138286 1.15 4.65 nucleic acid binding Eukaryotic translation initiation factor 3, subunit 9 eta, 116kDa (EIF3S9) NM_003751 -1.85 2.02 translation initiation factor activity; RNA binding Myocardin (MYOCD) NM_153604 -1.79 0.63 DNA binding Histone 4, H4 (HIST4H4) NM_175054 -1.19 2.45 DNA binding O. Receptors and binding genes Secreted frizzled-related protein 1 (SFRP1) NM_003012 2.55 0.63 transmembrane receptor activity  Coagulation factor II (thrombin) receptor (F2R) NM_001992 1.44 0.63 receptor binding; thrombin receptor activity Folate receptor 2 (fetal) (FOLR2) NM_000803 1.19 4.65 folic acid binding; receptor activity Mucin 4 (MUC4) NM_004532 -2.63 0.63 ErbB-2 class receptor binding Semaphorin Y (SEMA6C) NM_030913 -1.73 4.65 receptor activity Potassium channel tetramerisation domain containing 18 (KCTD18) NM_152387 -1.52 2.45 protein binding PDZ and LIM domain 7 (enigma) (PDLIM7) NM_005451 -1.36 4.01 protein binding P. Other genes Sorting nexin 16 (SNX16) NM_022133 1.63 4.65 intracellular signaling cascade Sestrin 3 (SESN3) NM_144665 1.39 2.02 cell cycle arrest Neuronal immediate early gene 1 (HOMER1) NM_004272 1.39 0.63 synaptic transmission Heat shock 22kDa protein 8 (HSPB8) NM_014365 -1.60 0.63 heat shock protein activity; kinase activity Small optic lobes homolog (Drosophila) (SOLH) NM_005632 -1.38 4.01 calpain activity Ras guanyl releasing protein 1 (RASGRP1) NM_005739 -1.34 2.45 Ras guanyl-nucleotide exchange factor activity Similar to common salivary protein 1 (hypothetical protein LOC124220) NM_145252 2.29 0.63 unknown Hypothetical protein FLJ35880 NM_153264 2.03 4.65 unknown Cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) NM_031476 1.61 2.45 unknown SH3-domain kinase binding protein 1 (SH3KBP1) NM_001024666 1.45 4.65 unknown Cingulin-like 1 (CGNL1) NM_032866 1.36 0.63 unknown Chromosome 10 open reading frame 58 (C10orf58) NM_032333 1.32 4.65 unknown Premature ovarian failure, 1B (POF1B) ^a NM_024921 1.27 / 1.23 2.45 / 4.65 unknown Ubiquitin-protein ligase E3-alpha (UBR1) NM_174916 1.27 4.01 unknown Similar to postmeiotic segregation increased 2-like 5 (LOC442329) XP_498220 1.26 4.65 unknown THUMP domain containing 1 (THUMPD1) NM_017736 1.20 4.65 unknown KIAA1160 protein NM_020701 -2.85 0.63 unknown Olfactomedin 4 (OLFM4) NM_006418 -2.44 2.02 unknown Calmodulin-like 1 (CALML1) GeneID: 809 -2.42 0.63 unknown  Zinc finger CCCH-type containing 12A (ZC3H12A) NM_025079 -2.37 0.63 unknown Chromosome 9 open reading frame 16 (C9orf16) NM_024112 -2.23 4.01 unknown Hypothetical protein FLJ13710 NM_024817 -2.14 0.63 unknown PDZK1 interacting protein 1 (PDZK1IP1) NM_005764 -1.89 0.63 unknown SEC 13-related protein (SEC13L1) NM_030673 -1.86 0.63 unknown Latent transforming growth factor beta binding protein 4 (LTBP4) ^a NM_003573 -1.80 / -1.67 / -1.61 0.63 / 4.01 / 0.63 unknown Chromosome 20 open reading frame 129 (C20orf129) NM_030919 -1.79 2.45 unknown Carboxyl ester lipase pseudogene (CELP) NR_001275 -1.71 0.63 unknown Family with sequence similarity 57, member B (FAM57B) NM_031478 -1.68 0.63 unknown LIM domain containing preferred translocation partner in lipoma (LPP) NM_005578 -1.62 2.45 unknown Torsin family 2, member A (TOR2A) NM_130459 -1.62 4.01 unknown Proteasome (prosome, macropain) 26S subunit, non-ATPase, 4 (PSMD4) NM_002810 -1.56 0.63 unknown Chromosome 20 open reading frame 133 (C20orf133) NM_080676 -1.48 2.02 unknown BENE protein (BENE) NM_005434 -1.41 2.45 unknown G protein-coupled receptor 172B (GPR172B) NM_017986 -1.35 4.65 unknown GPI-anchored metastasis-associated protein homolog (C4.4A) NM_014400 -1.29 4.65 unknown Epidermal growth factor receptor pathway substrate 8-related protein 1 (EPS8R1), isoform B NM_017729 -1.25 4.65 unknown Thymus expressed gene 3-like (MGC15476) NM_145056 -1.24 2.45 unknown Tribbles homolog 2 (TRIB2) NM_021643 -1.16 4.01 unknown

^a Multiple-primers designed on the same gene

Among the candidate genes listed in Table 2 above, several characteristic genes such as FceRI, SPINK5, CCL18, cathepsin G (CTSG), VCAM1, tenascin C (TNC), and phospholipase A2 (PLA2G4C), and atopic dermatitis development Several ECM genes known to be associated with were detected in this example in accordance with previous studies.

2. Class 1: ECM ( extracellular  matrix) And cell adhesion genes

Upregulation patterns of ECM and cell adhesion related genes were most observed in exogenous atopic dermatitis patients (18 of the candidate genes detected were upregulated, see Table 2). In addition, other ECM genes, such as the collagen genes COL1A1, COL1A2, COL3A1, COL12A1, COL15A1, were detected to be upregulated in exogenous atopic dermatitis patients. Deposition of collagen types I and III is known to be involved in the recovery process during remodeling of the skin lesions of patients with atopic dermatitis, and these collagen genes are reported to decrease after UV A1 phototherapy. appear.

3. Class 2: cytokines, chemokines and related genes

Cytokines and chemokines are known to be associated with the development of atopic dermatitis, in particular Th2 cell responses and B cell mediated IgE production. As shown in Table 2, CCL18 and CXCL14 are upregulated while IL1F9, IFNA1 and IL1F6 are downregulated. CCL18 has been reported to be more than two-fold upregulated in atopic dermatitis skin as compared to psoriasis skin, and superantigen staphylococcal enterotoxin B and allergen in patients with atopic dermatitis It is known to be significantly induced by exposure.

4. Classification 3: Antimicrobial Peptide  And immune response genes

Antimicrobial peptides are known to be involved in inflammatory responses to external microbial infections in atopic dermatitis patients. In this example, CTSL2 and CTSG are up-regulated and DEFB4 are down-regulated in atopic dermatitis skin. During UVA phototherapy, CTSG is reported to be down-regulated by UVA irradiation in skin inflammatory infiltrates in patients with severe atopic dermatitis [Breuckmann F et al .: Modulation of cathepsin G expression in severe atopic dermatitis following medium-dose UVA1 phototherapy. BMC Dermatol 2: 12, 2002]. Downregulation of DEFB4 is thought to reduce the skin's defense against microbial infection, which is thought to cause susceptibility to infection.

5. Class 4: Proteolytic Enzymes and Inhibitors thereof

Proteases, such as serine proteases, chymases, tryptases and chymotrypsin enzymes, are known to contribute to the development of chronic inflammatory atopic dermatitis. These proteases are thought to be associated with atopic pruritus and are suggested to be able to treat atopic dermatitis by their inhibitors. In this example several interesting genes were detected: CPA3, TPSAB1, CST6 and CPVL are upregulated; TMPRSS11D, KLKs (4, 6, 8 and 14), SERPINBs (3, 12 and 13), PLAT, CSTA, SHH, PRSS3 and USP11 were down regulated.

6. Class 5: lipid-related genes

Abnormalities in lipid-related genes may cause skin dryness in patients with atopic dermatitis. Dry skin is a direct cause of itching. In this example the following lipid related genes were detected: THRSP, PLA2G4C, PLA2R1, FADS2, Zn-alpha-2-GP and FABP7 are upregulated; CRABP2, FABP5, GM2A, LDLR, GLTP and MAL are downregulated. Interestingly, PLA2G4C and its receptor were simultaneously detected to show upregulation patterns. Previous reports indicate that increased activity of PLA2G4C is detected in the atopic epidermis, indicating an incomplete conversion of phospholipids to other lipid forms. Another report supports the fact that PLA2G4C is involved in atopic dermatitis, suggesting the potential of PLA2G4C inhibitors for the treatment of inflammatory skin diseases.

In addition to the genes classified above, other genes include metal binding genes, hormone-related genes, ATP / GTP binding genes, structural genes, heparin binding genes, transcription genes, transport genes, various metabolic enzyme genes, nucleic acid binding genes and receptors or binding genes. And the like (see Table 2).

7. RT- between normal controls and patients with exogenous atopic dermatitis PCR  compare

RT-PCR was performed to qualitatively compare expression levels between normal and exogenous atopic dermatitis samples and the results are shown in FIG. 2. In Figure 2, FceRI is a high affinity immunoglobulin epsilon receptor alpha-subunit, FABP7 is a fatty acid-binding protein 7, CPA3 is a carboxypeptidase A3 , ARSF for arylsulfatase F, AREG for amphiregulin, GJB2 for gap junction protein beta 2, 26 kDa, GLTP for glycolipid transfer protein glycolipid transfer protein), HAS3 means hyaluronan synthase 3, HIST4H4 means histone 4 (Hystone 4, H4), GAPDH was used as relative quality control, and PCRs were randomized pairing Was performed by.

As shown in FIG. 2, FceRI, the most important marker of exogenous atopic dermatitis, was found to be significantly upregulated (see a in FIG. 2). In addition, in exogenous atopic dermatitis samples, FABP7 and CPA3 were up regulated (see b in FIG. 2) and ARSF, AREG, GJB2, GLTP, HAS3 and HIST4H4 were down regulated (see c in FIG. 2). This result is consistent with the microarray result data.

8. PEIMAP  (protein experimental interactome  map and PSIMAP (protein structural) interactome  protein-protein interactions through maps, PPI ) prediction

PPI prediction was performed using the 205 candidate genes in Table 2. 104 genes were found to have 458 interaction partners in total (each gene with an average of 8 interaction partners). Herbal genes of exogenous atopic dermatitis that exhibit high interaction scores (see FIG. 3) can be functionally classified as follows: 1) ECM and cell adhesion-related genes (TNC, VCAM1, CXADR) , CEACAM5, COL12A1), 2) ATP / GTP binding gene (NTRK2), 3) immune response genes (FceRI, CTSG, CD200R1), 4) proteolytic enzymes (KLK4, KLK6, KLK8, KLK14, TMPRSS11D, PLAT), and 5) structural genes (CDON, ACTG2).

3 shows PPI mapping results: (3a) PEIMAP; (3b) PSIMAP; And (3c) overlapping maps of PEIMAP and PSIMAP. Those labeled in red and blue represent herbal proteins. Red protein is defined as a protein that interacts with at least 25% of the total protein in the network. Blue proteins are proteins that interact with 20-25% of the total protein in the network. In addition, the edge thickness between the two proteins represents the number of reference databases. The data are from Table 2.

These genes were obtained as a result of overlapping PEIMAP (see FIG. 3A) and PSIMAP (see FIG. 3B) (see FIG. 3C). Several herb genes such as FceRI, VCAM1, TNC, and CTSG were found to be associated with the development of atopic dermatitis. In addition, other herbal genes were also found to be associated with the development of atopic dermatitis, which include CDON (Surface glycoprotein, Ig superfamily member), ACTG2 (Actin, gamma 2), and NTRK2 (BDNF / NT-3 growth factors receptor precursors). This suggests that the predicted interactions can be used to analyze the molecular mechanisms of genes known to be associated with the development of atopic dermatitis, as well as newly known genes.

3.9. Biochemical Pathway Analysis and Physiological Prediction

Biochemical pathways were analyzed for 94 up-regulated genes and 109 down-regulated genes as genes with more than two-fold changes in expression levels. The up-regulated and down-regulated genes have been assigned to various annotations in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway [Kanehisa M et al .: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28: 27 30, 2000.]. Detailed information is shown in Tables 3 and 4 below (number of genes and P-values in the KEGG pathway). P-value significance was assessed by DAVID [Huang DW et al .: The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol 8 : R183, 2007].

TABLE 3 KEGG pathway mapping results for upregulated genes

Pathway Description Number of genes P-value Cell communication 7 2.70E-04 Focal adhesion 5 7.70E-02 ECM-receptor interaction 4 3.10E-02 Leukocyte transendothelial migration 4 6.10E-02 PPAR signaling pathway 4 N / A TGF-beta signaling pathway 3 N / A Tight junction 3 N / A Cell adhesion molecules (CAMs) 2 N / A Cytokine-cytokine receptor interaction 2 N / A Hematopoietic cell lineage 2 N / A Metabolism of xenobiotics by cytochrome P450 2 N / A Neuroactive ligand-receptor interaction 2 N / A Pathogenic Escherichia coli infection-ehec 2 N / A Pathogenic Escherichia coli infection-epec 2 N / A Renin-angiotensin system 2 N / A MAPK signaling pathway One N / A Regulation of actin cytoskeleton One N / A

TABLE 4 KEGG Pathway Mapping Results for Downregulated Genes

Pathway Description Number of genes P-value MAPK signaling pathway 4 N / A Cell communication 3 N / A Regulation of actin cytoskeleton 3 N / A Toll-like receptor signaling pathway 3 N / A Axon guidance 2 N / A B cell receptor signaling pathway 2 N / A Bile acid biosynthesis 2 N / A Calcium signaling pathway 2 N / A Colorectal cancer 2 N / A Epithelial cell signaling in Helicobacter pylori infection 2 N / A ErbB signaling pathway 2 N / A Focal adhesion 2 N / A Galactose metabolism 2 N / A Linoleic acid metabolism 2 N / A Natural killer cell mediated cytotoxicity 2 N / A Pancreatic cancer 2 N / A Renal cell carcinoma 2 N / A T cell receptor signaling pathway 2 N / A Valine, leucine and isoleucine degradation 2 N / A Leukocyte transendothelial migration One N / A

Upregulated genes were assigned to the following pathways: cell communication (7), focal adhesion (5), ECM-receptor interaction (4), And leukocyte transdermal migration (leukocyte transendothelial migration, four). In addition, down-regulated genes were assigned to the following pathways: MAPK signaling pathway (four), intercellular communication (three), and regulation of actin cytoskeleton (three). ), And toll-like receptor signaling pathways (three).

Physicochemical characterization was performed on 205 candidate genes. As a result, several genes were found to be included in the membrane domain. These genes are IFI27 (Interferon), MAL (T-cell differentiation protein), BENE (unknown), and GPR172B (unknown). To predict physiochemical properties, Biopython package (www.biopython.org; grave score, hydropathy, and IEP modules), Phobius [Kal L et al .: A combined transmembrane topology and signal peptide prediction method. J Mol Biol 338 : 1027 1036, 2004], and Localizome [Lee S et al .: Localizome: a server for identifying transmembrane topologies and TM helices of eukaryotic proteins utilizing domain information. Nucleic Acids Res 34 : W99 W103, 200] was used. The BENE and GPR172B genes have not yet been functionally identified, and therefore these genes are considered to be important candidate genes (see Table 5).

Table 5 Physiological and Chemical Properties of Differently Modified Genes

Gene symbol Length Weight Instability IEP Gravyscore Membrane IFI27 119 13394.15 32.64 11.07 1.23 yes MAL 153 19451.97 37.66 5.55 1.01 yes BENE 153 20088.82 48.48 6.14 0.86 yes GPR172B 448 54426.06 44.88 6.04 0.8 yes SLC7A5 507 64126.41 37.79 7.9 0.74 yes SLC5A6 635 80124.25 38.21 8.61 0.67 yes SLC39A2 309 38300.37 43.03 5.98 0.66 yes KDELR3 214 28864.28 31.59 9.07 0.61 yes DEFB4 64 8172.72 41.31 9.46 0.6 no SLC16A10 515 64752.78 37.74 7.87 0.54 yes FAM57B 274 35547.75 38.96 9.12 0.47 yes F2R 425 55049.06 46.62 8.65 0.46 yes RHCG 479 61790.64 30.32 5.93 0.46 yes SLC16A14 510 65424.13 41.34 6.45 0.45 yes Zn-alpha-2-GP 107 14207.09 68.17 6.16 0.45 yes SLC1A2 574 72427.53 35.37 6.09 0.43 yes CLDN10 228 28577.9 26.7 8.32 0.36 yes GJB2 226 30268.71 42.8 9.11 0.29 yes PDZK1IP1 114 14262.86 56.91 4.79 0.26 yes GM2A 193 24297.46 42.29 5.17 0.2 no SOAT1 550 74625.2 36.71 9.08 0.19 yes HAS3 553 72943.14 46.91 8.77 0.19 yes MGST1 155 20373.06 24.82 9.41 0.19 yes

3.10. Possible promoter and coding regions of candidate genes SNPs  (Single Nucleotide Polymorphisms )

In order to determine genetic variability on candidate genes, SNPs of promoters, coding sites and splice sites were searched. TRANSPAC 8.4 [Matys V et al .: TRANSFAC: transcriptional regulation, from patterns to profiles. Nucleic Acids Res 31 : 374 378, 2003] and SNP @ Promoter database [Kim BC et al. SNP @ Promoter: a database of human SNPs (Single Nucleotide Polymorphisms) within the putative promoter region. The promoter information given by BMC Bioinformatics 9 : S2, 2008] was used to select the upstream 1 kb region of each gene to be used for SNPs detection. To search for other non-synonymous SNPs for coding and splice sites, dbSNP [Sherry ST et al .: dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29 : 308 311, 2001] version 126 was used. Four splice site SNPs were searched for the SERPINB13 (rs45958880), COL1A2 (rs1799871), CPA3 (rs7635943), and TGM1 (rs2854998) genes. RefSNP (rs) is the reference SNP of the dbSNP database. Among the candidate genes, 724 non-identical SNPs and 211 promoter SNPs were searched. Among the herb genes, TNC (Tenascin C) and CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) had the largest number of (10) non-homologous SNPs. In addition, SNPs of the KLK6 (Kallikrein 6) gene (rs12459365, rs11671058) are known to be associated with atopic dermatitis (see GAD database, Becker KG et al .: The genetic association database. Nat Genet 36 : 431 432, 2004). ARG1 (Arginase) is known also associated with atopic dermatitis SNPs (rs2781664, rs2781663) of the gene (HGMD referenced database, Stenson PD such as: HGMD Human gene Mutation database (HGMD ): 2003 update Hum Mutat 21:. 577 581, 2003 Thus, atopic dermatitis specific SNPs are useful for analyzing genetically modified genes as atopic dermatitis gene markers (see Table 6).

Table 6 Number of SNPs in Herbal Genes

Gene symbol RefID SNPs in TFsite (rs number) ^a Non-synonymous SNPs
(rs number) ^a TNC NM_002160 - rs13321, rs2274750, rs2104772, rs3748169, rs3748170, rs1061494, rs7020958, rs1061493, rs1757095, rs3827816 VCAM1 NM_001078 rs3783606, rs3170794, rs3170794 rs3783615,34199378, rs34100871, rs3783613, rs3783612, rs3783611, rs34708918, rs34228330 CXADR NM_001338 - rs34727960 CEACAM5 NM_004363 - rs11545767, rs10423171, s7249230, rs10407503, rs17853315, rs3815780, rs35091611, rs34155934, rs28683503, rs12971352 COL12A1 NM_004370 - rs970547, rs34846477, rs34369939, rs35710072, rs35523808, rs34336755, rs34438461, rs240736,
rs34730529 NTRK2 NM_001007097 rs1187321 rs2275857, rs1047856 FceRI NM_002001 - rs17851282, rs2298805, rs2298804 CD200R1 NM_138806 - rs9865242, rs9826308, rs34985808, rs2171509, rs4596117 KLK4 NM_004917 rs2979452 rs34626614, rs2569527, rs1654551 KLK6 NM_001012964 rs11671058 - KLK8 NM_007196 - rs17854057, rs16988799 KLK14 NM_022046 rs7259389, rs7259389 rs35287116, rs2569491, rs2569490 PLAT NM_000930 rs8178872, rs8178674, rs8178672, rs8178672,
rs2854290, rs2854290, rs13306819 rs1804182,8178747, 8178748,2020921, rs3020630,8178733 CDON NM_016952 - rs684535, rs12274923, rs35665264, rs3740909, rs7122277, rs3740912 ACTG2 NM_001615 rs831533 rs3209900, rs3190470

^a rs number: the reference SNP number of the dbSNP database

1 shows the results of cDNA microarray analysis of biopsy tissue obtained from exogenous atopic dermatitis patients.

Figure 2 shows the RT-PCR results.

Figure 3 shows the protein-protein interaction (PPI) mapping results, 3a shows the PEIMAP, 3b shows the PSIMAP, 3c shows the overlapping map of PEIMAP and PSIMAP.

<110> SAMSUNG LIFE PUBLIC WELFARE FOUNDATION SAMSUNG MEDICAL CENTER <120> BIOMARKER FOR EXTRINSIC TYPE ATOPIC DERMATITIS <160> 18 <170> KopatentIn 1.71 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for Fc fragment of IgE high affinity I receptor          (FceRI) <400> 1 tgtggcagct ggactatgag 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Reverse primer for Fc fragment of IgE high affinity I receptor          (FceRI) <400> 2 caattgctga tgctggaaaa 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for Fatty acid binding protein 7, brain (FABP7) <400> 3 ccagctggga gaagagtttg 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> Reverse primer for Fatty acid binding protein 7, brain (FABP7) <400> 4 ctcatagtgg cgaacagcaa 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for Carboxypeptidase A3 (CPA3) <400> 5 acttggccaa aaccaatgag 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> Reverse primer for Carboxypeptidase A3 (CPA3) <400> 6 tccaagccac aatcttttcc 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for Arylsulfatase F (ARSF) <400> 7 ggacgacagt gggtcagttt 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> Reverse primer for Arylsulfatase F (ARSF) <400> 8 gtgtcagggg tgtggactct 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for Amphiregulin (AREG) <400> 9 aagcgtgaac cattttctgg 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> Reverse primer for Amphiregulin (AREG) <400> 10 ccatttttgc ctcccttttt 20 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for Gap junction protein, beta 2 (GJB2) <400> 11 actccaccag cattggaaag 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Reverse primer for Gap junction protein, beta 2 (GJB2) <400> 12 tgggagatgg ggaagtagtg 20 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for Glycolipid transfer protein (GLTP) <400> 13 tcctggaggt ggagaaagaa 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> Reverse primer for Glycolipid transfer protein (GLTP) <400> 14 taacattctg ccccttggag 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for Hyaluronan synthase 3 (HAS3) <400> 15 gtcagtggtc acgggtttct 20 <210> 16 <211> 20 <212> DNA <213> Artificial Sequence <220> Reverse primer for Hyaluronan synthase 3 (HAS3) <400> 16 aggccaatga agttcaccac 20 <210> 17 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for Histone 4, H4 (HIST4H4) <400> 17 aagcgcattt ctggtctcat 20 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> Reverse primer for Histone 4, H4 (HIST4H4) <400> 18 aagggccttt tggagtctgt 20  

Claims (10)

Oligonucleotide probes having sequences complementary to mRNA obtained from the GLTP (NM_016433) gene; And An antibody for detecting a protein encoded by the gene; At least one selected from the group consisting of Exogenous atopic skin disease diagnostic composition. The composition of claim 1, wherein the composition is further IFI27 (NM_005532), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), KDELR3 (NM_006855), SLC16A10 (NM_018593), FAM57B (NM_0RN_M_1992R) SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171), CLDN10 (NM_006984), GJB2 (NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_000405), SOAT1 (NM533) And oligonucleotide probes having sequences complementary to mRNA obtained from one or more genes selected from the group consisting of MGST1 (NM_020300); An antibody for detecting a protein encoded by said one or more genes; And rs3783606, rs3170794, rs3170794, rs3783615,34199378, rs34100871, rs3783613, rs3783612, rs3783611, rs34708918, rs34228330, rs970547, rs34846477, rs34369939, rs35710072, rs35523808, rs34336755, rs34438461, rs240736, rs34730529, rs1187321, rs2275857, rs1047856, rs9865242, rs9826308, rs34985808, rs2171509, rs4596117, rs2979452, rs34626614, rs2569527, rs1654551, rs8178872, rs8178674, rs8178672, rs8178672, rs2854290, rs2854290, rs13306819, rs1804182, rs8178747, rs8178748, rs2020921, rs3020630, rs8178733, rs684535, rs12274923, rs35665264, rs3740909, rs7122277, Probes for the detection of one or more SNPs selected from the group consisting of rs3740912, rs831533, rs3209900, and rs3190470 To include one or more selected from the group consisting of Exogenous atopic skin disease diagnostic composition. Biochip for diagnosing exogenous atopic skin disease comprising the composition of claim 1 or 2. To provide the information necessary for the diagnosis of exogenous atopic dermatological diseases, the expression level of the exogenous atopic dermatitis marker GLTP (NM_016433) gene was measured in a sample obtained from a subject and compared with the expression level of the gene in normal individuals. A method for detecting an exogenous atopic skin disease marker, comprising the step of: The method of claim 4, further In samples obtained from subjects, IFI27 (NM_005532), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), KDELR3 (NM_006855), SLC16A10 (N_0_0M93), FR57N (M_1992) , RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171), CLDN10 (NM_006984), GJB2 (NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_101) ), HAS3 (NM_005329), and MGST1 (NM_020300) comprising the steps of measuring the expression level of one or more exogenous atopic skin disease marker gene selected from the group consisting of and comparing it with the expression level of the gene in normal individuals That, A method for detecting exogenous atopic skin disease markers. The method of claim 4, further Rs3783606, rs3170794, rs3170794, rs3783615,34199378, rs34100871, rs3783613, rs3783612, rs3783611, rs34708918, rs34228330, rs970547, rs34846477, rs34755, rs355 rs1047856, rs9865242, rs9826308, rs34985808, rs2171509, rs4596117, rs2979452, rs34626614, rs2569527, rs1654551, rs8178872, rs8178674, rs8178672, rs8178672, rs2854290, rs2854290, rs13306819, rs1804182, rs8178747, rs8178748, rs2020921, rs3020630, rs8178733, rs684535, rs12274923, measuring the presence of at least one exogenous atopic skin disease marker SNP selected from the group consisting of rs35665264, rs3740909, rs7122277, rs3740912, rs831533, rs3209900, and rs3190470, A method for detecting exogenous atopic skin disease markers. Contacting the candidate with a biopsy sample; Measuring the expression level of the GLTP (NM_016433) gene in the candidate-contacted sample; Comparing the expression level measured in the sample contacted with the candidate with the expression level of the gene in the sample not contacted with the candidate; And If the expression level of GLTP (NM_016433) in the sample contacted with the result of the comparison is reduced compared to the normal subject, judging the candidate substance as a cause of exogenous atopic skin disease Exogenous atopic skin disease triggers search method comprising a. The method of claim 7, further comprising Contacting the candidate with a biopsy sample; IFI27 (NM_005532), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), KDELR3 (NM_006855), SLC16A10 (N_0_0185), FR57 (NM_018593) NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171), CLDN10 (NM_006984), GJB2 (NM_004004), PDZK1IP1 (NM_005764), M_000000 Measuring the expression level of one or more genes selected from the group consisting of (NM_003101), HAS3 (NM_005329), and MGST1 (NM_020300); Comparing the expression level measured in the sample contacted with the candidate with the expression level of the gene in the sample not contacted with the candidate; And As a result of the comparison, KDELR3 (NM_006855), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171), CLDN10 (NM_006984) , At least one expression level selected from the group consisting of, SOAT1 (NM_003101), and MGST1 (NM_020300) is increased compared to normal individuals, or IFI27 (NM_005532), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095 ), SLC39A2 (NM_014579), SLC16A10 (NM_018593), FAM57B (NM_031478), GJB2 (NM_004004), PDZK1IP1 (NM_005764), GM2A (NM_000405), and HAS3 (NM_005329). Determining the candidate substance as the cause of exogenous atopic dermatitis when reduced in comparison with Exogenous atopic skin disease triggers search method comprising a. Contacting the candidate with a sample obtained from an exogenous atopic skin disease patient; Measuring the expression level of GLTP (NM_016433) in the candidate-contacted sample; Comparing the expression level measured in the sample of the atopic skin disease patient contacted with the candidate with the expression level of the corresponding gene in the sample of the atopic skin disease patient not contacted with the candidate; And As a result of the comparison, when the expression level of GLTP (NM_016433) in the sample contacted with the candidate substance is increased than the expression level of the gene in the sample without contact with the candidate substance, the candidate substance is used as a prophylactic or therapeutic substance for exogenous atopic skin disease. Judgment Step Search for a method for preventing, alleviating or treating exogenous atopic dermatological diseases comprising a. 10. The method of claim 9, Additionally Contacting the candidate with a sample obtained from an exogenous atopic skin disease patient; IFI27 (NM_005532), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), KDELR3 (NM_006855), SLC16A10 (N_0_0185), FR57 (NM_018593) NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171), CLDN10 (NM_006984), GJB2 (NM_004004), PDZK1IP1 (NM_005764), M_000000 Measuring at least one expression level selected from the group consisting of (NM_003101), HAS3 (NM_005329), and MGST1 (NM_020300); Comparing the expression level measured in the sample of the atopic skin disease patient contacted with the candidate with the expression level of the corresponding gene in the sample of the atopic skin disease patient not contacted with the candidate; And As a result of the comparison, KDELR3 (NM_006855), F2R (NM_001992), RHCG (NM_016321), SLC16A14 (NM_152527), Zn-alpha-2-GP (XM_379897), SLC1A2 (NM_004171), CLDN10 (NM_006984) , The level of expression of one or more selected from the group consisting of SOAT1 (NM_003101), and MGST1 (NM_020300) is less than the expression level of the gene in the sample without contact with the candidate, or IFI27 (in the sample contacted with the candidate). NM_005532), GPR172B (NM_017986), SLC7A5 (NM_003486), SLC5A6 (NM_021095), SLC39A2 (NM_014579), SLC16A10 (NM_018593), FAM57B (NM_031478), GJB2 (NM_004004)) PDN2 (NM_005329) when the level of expression of one or more selected from the group consisting of more than the expression level of the gene in a sample that is not in contact with the candidate, judging the candidate as a prophylactic or therapeutic substance for exogenous atopic skin diseases Search for a method for preventing, alleviating or treating exogenous atopic dermatological diseases comprising a.

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