Variants in MHC, LCE and IL12B have epistatic effects on psoriasis risk in Chinese population.

BACKGROUND:Psoriasis has long been considered as a complex disease, and gene-gene or gene-environment interactions may jointly influence the etiology for psoriasis. OBJECTIVE:We evaluated the associations of single nucleotide polymorphisms (SNPs) in MHC region, and determined the epistasis and combined effects of MHC locus and IL12B, LCE on risk for psoriasis. METHODS:We genotyped SNP rs1265181 (MHC) in 5067 cases and 6404 controls, combining with the prior GWAS data (1139 cases and 1132 controls), we explored the genetic interaction among MHC locus, LCE and IL12B by using logistic regression analysis. We evaluated the combined effects of MHC locus and two non-MHC loci in the combined sample of 6206 cases and 7536 controls. RESULTS:Extremely high significance of association was detected between rs1265181 and psoriasis (p combined < 10E--300, OR = 16.52, 95% CI: 15.28-18.44). We observed significant interactions between MHC and LCE (p = 0.0016) and between MHC and IL12B (p = 0.0036). The risk increased some 26-fold in individuals with risk alleles in both MHC and LCE as compared with those without risk alleles, and individual carrying risk alleles of MHC and IL12B has around 36-fold higher risk of psoriasis than those with protective alleles. CONCLUSIONS:This study provides evidence for the epistatic effects between MHC locus and LCE, IL12B genes. Besides, we suggest that MHC might be the main effect gene on the risk for psoriasis. This data may contribute to our understanding of psoriasis genetic interactions and account for the additional risk of certain patients to develop psoriasis.

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