Gene-gene Interactions Between ERAP1, TRAF3IP2,TNFAIP3and HLA-C To The Risk Of Psoriasis In Chinese Han

Background Psoriasis is a common immune-mediated skin disorder affecting almost0.2-2%populations worldwide. The typical clinical features include epidermal hyper-proliferation, vascular remodeling and inflammation. It is strongly believed that there is complex genetic and environmental etiology underlying psoriasis. Gene-gene and gene-environment interactions are thought to play important roles in this complex pathogenesis. In recent years, almost50susceptible genes have been identified in psoriasis through Genome Wide Association Studies (GWASs) in diverse populations. Among these findings, several key genes exhibited important roles in the development of psoriasis, such as HLA-C, ERAP1, TNFAIP3and TRAP3IP2through NF-κB pathway or IL17signaling. Moreover, three findings in gene-gene interactions between HLA-C and ERAP1, TNFAIP3and HLA-C, HLA-C and TRAF3IP2in Western ethnic were revealed, greatly deepening the understandings of genetic architecture for psoriasis. In order to validate these interactive findings in Chinese Han, we performed this research.Objectives To study three gene-gene interaction findings which were established by previous studies in Caucasian psoriasis.Methods The genotyping data for five SNPs (rs1265181in MHC locus, rs151823in ERAP1, rs240993in TRAF3IP2, rs640353and rs610604in TNFAIP3) was extracted from our previous GWAS data in psoriasis, performed by Illumina Whole Genome Genotyping in2833samples and validation data on these5SNPs. The genotyping were carried out on Illumina Human610-Quad BeadChips and validated on Sequenom MassArray system (Sequenom iPLEX Assay) at The Key Laboratory of Dermatology, Ministry of Education, Hefei, Anhui, China according to manufacturer’s instructions. These genotyping procedures have been described elsewhere. After stringent quality control procedures4747Chinese Han psoriasis cases and7104healthy controls were included. The best-fit association models were identified through Chi-square test in Plink1.07. The genotype was coded as0,1,2for harboring0,1,2risk allele(s) respectively in additive model. It was coded as0,1for whether taking risk allele in dominant model. It was coded as1for whether two risk alleles under recessive model, else coded as0. Unconditional logistic regression analysis was applied to explore the two-way epistasis effect, based on likelihood ratio statistic test. The corresponding p value was calculated for testing interaction. The statistical significant level is a two-sided of0.05for all tests. The above analyses were conducted in Stata10.0(StataCorp, College Station, TX).Results A significant pair-wise gene-gene interaction between rs1265181and rs151823was established in Chinese Han (chisq=17.36, p=0.0002). The joint effect showed that the risk of psoriasis increased greatly when only with one risk allele of rs1265181(ORs were17.73,24.8and,25.24respectively). There was no interactive evidences between rs240993and rs1265181(chisq=2.41,p=0.3004); Nevertheless, our study did not find any positive epistastic result between TNFAIP3and HLA-C for rs640353and rsl265181(chisq=0.24, p=0.6228) and for rs610604and rsl265181(chisq=0.68, p=0.8773).Conclusion Our study confirmed two gene-gene interaction results in Chinese Han, failed to confirm the other gene interactions, highlighting the genetic heterogeneity in gene interaction between diverse populations.