Combined effect of five single nucleotide polymorphisms related to IL23/Th17 pathway in the risk of psoriasis

Psoriasis is a common immune-mediated inflammatory skin disease with strong genetic components, in which the IL23/Th17 pathway has been implicated. To explore the effective role in psoriasis, we genotyped five single nucleotide polymorphisms in genes related to IL23/Th17 pathway in 14,929 Han Chinese samples. A Bonferroni-corrected significant single-variant association was identified between rs1512970 within IL21 (odds ratio (OR) = 1.07, 95 % confidence interval (CI) = 1.02-1.13, P = 4.94 x 10(-03)). We failed to validate rs744166 (OR = 1.06, 95 % CI = 1.01-1.11, P = 1.52 x 10(-02)) and other three SNPs (P = 2.48 x 10(-01) similar to aEuro parts per thousand 1.27 x 10(-02)) to meet the single-variant association significance threshold. However, we found that their combined effect substantially contributed to the risk of psoriasis in our sample (P = 3.91 x 10(-07)) and the highest score group conferred the largest risk effect size (OR = 1.22, 95 % CI = 1.11-1.34, P = 1.85 x 10(-05)). Our results implicate the ethnic heterogeneity in the susceptibility of psoriasis and suggest common variants with weak effect in IL23/Th17 pathway, which do not show significance in conventional single-variant association study, may contribute to the risk of psoriasis. This study sheds light on the important role of IL23/Th17 pathway in the susceptibility of psoriasis.