Association Study On Allergic Sensitization Susceptibility Gene In Chinese Atopic Dermatisis Population

Background Atopic Dermatisis(AD) is a common chronic inflammatory skindisease, the disease clinical features including with early onset age on children andoften relapse. As we known AD patients often occur asthma, allergic rhinitis, foodallergy and serum IgE elevated in their later life. Its etiology and pathogenesis remainsunclear so far. It has proved that genetic factors is the main factor of AD susceptibilitythrough the large population, pedigree and twins studies all over the world. The AD,allergic rhinitis and asthma are belonged to the atopic diseases, which might share somecommon genetic hererogeneity. In recent years, foreign studies had found a number ofsusceptibility loci associated with asthma, allergic rhinitis and other allergic disease. Aswe know, AD patients often accompany with asthma, allergic rhinitis and other allergicdisease. So it is necessary to do research on the association between allergic diseasesusceptibility loci and AD. This study will provide a new theoretical basis fordiscovering AD and other allergic predisposition population, susceptible target genes,risk assessment, clinical diagnosis and treatment and drug development.Objective The previous10SNPs were reported as susceptibility loci for allergicdiseases in foreign population were investigated in Chinese Han population,2SNPswere reported to associated with AD as well. After genotyping by Sequenom platform,we did a further genotype and phenotype analysis based on the result of Sequenomgenotyping. These clinical features including onset age, family atopic history, diseaseseverity base on SCORAD, concomitish with ashma and(or) allergic rhinitis, serum IgE elevated and so on. Our research may rich the previous AD genotype and phenotypedatabases.Methods1.We selected ten SNPs from foreign reports of allergic diseases and2SNPswere reported to associate with AD. Then carried out a Sequenom genotyping in3,013atopic dermatitis cases and5,483controls for the loci and SNPs from our selection.The cases and controls are matched in race and region.2.The clinical data of the cases were stratified by onset age, family atopic history andConcomitant diseases. The PLINK1.07statistical package was applied to analysis thegenotype and phenotype clinical features including onset age, family atopic history,disease severity base on SCORAD, concomitish with ashma and(or) allergic rhinitis,serum IgE elevated and so on between each SNP between cases and controls, casesand cases. Investigated the relationship between every loci-allele and the diseaseclinical phenotype. Ultimately identified the risk genotype of AD.Results Three of the12SNPs showed some association with AD, includingrs16999165（P=0.0186；OR=0.922） at CYP24A1/PFDN4(20q13) was reportedassociate with AD,rs1837253（P=0.0352；OR=0.936） at TSLP（5q22.1） was reportedas susceptible gene for athsma, AR and other allergic disease. rs2158177（P=0.0428；OR=1.09） was located in RAD50/IL13gene and associated with AD overlappingeffects on asthma and psoriasis. Allele and genotype-penotype analysis showed thatrs1837253associated with AD phenotype, while the other two SNPs without anymeaningful discovery.2. Allelic association analysis of rs1837253was significantly different between cases.(1) AD with palmar hyperlinearity: SNP rs1837253showed a significantly differencebetween cases of AD with palmar hyperlinearity and without palmar hyperlinearity (P=0.003), comparative association between AD with palmar hyperlinearity andcontrols(P=4.5E-05), AD without palmar hyperlinearity and controls(P=0.107);（2）Disease severity: Allelic analysis of rs1837253showed a significantly associationbetween severity cases and mild/moderate cases(P=0.017),severity cases andcontrols(P=1.93E-04),mild/moderate cases and controls(P=0.266).（3） AD with allergic rhinitis： the difference of MAF between cases wassignificant(P=0.035), the difference between AD with allergic rhinitis and controls wasalso significant(P=0.001), there showed no significant difference between AD withoutallergic rhinitis and controls(P=0.166).3. Genotypic analysis of rs1837253between cases and controls.(1) For AD with palmar hyperlinearity, the difference in distribution of rs18372532C/Tgenotype between the cases and “cases only” was statistically significant(PCC=2.92E-04,OR=0.56).(2) For the disease severity(SCORAD) between Mild/Moderate and severity thestatistical distribution of genotype was significant(PCC=0.01,OR=0.723).(3) for AD with allergic rhinintis the difference in distribution of genotype was alsosignificant(PCC=0.054,OR=0.854).Conclusions (1) There are some common susceptibility loci for allergic diseases andAD, it need more research on the association of common mechanisms between AD andother atopic diseases.(2) TSLP is not only associated with asthma and atopic dermatisis,may also be susceptibility genes for AD. The SNP rs1837253may associate with theclinical phenotypes of AD:①SNP rs1837253significantly associated with pattern of ADwith palmar hyperlinearity(P=0.003,OR=0.81), and the CC genotype play a protectiverole for this phenotype;②This SNP was also associated with disease clinicalphenotype of AD with allergic rhinitis, but failed to find the significant protective or risk genotype;③SNP rs1837253was associated with the disease severity of AD,genotype CC may be associated with its clinical type.