title: Combined effect of five single nucleotide polymorphisms related to IL23/Th17 pathway in the risk of psoriasis.
abstract: 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 × 10(-03)). We failed to validate rs744166 (OR = 1.06, 95 % CI = 1.01-1.11, P = 1.52 × 10(-02)) and other three SNPs (P = 2.48 × 10(-01) ∼ 1.27 × 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 × 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 × 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.
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230032, China, xianyongyin@gmail.com.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Yin
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Xing
authors.initials: X
authors.lastname: Fan
authors.forename: Fusheng
authors.initials: F
authors.lastname: Zhou
authors.forename: Long
authors.initials: L
authors.lastname: Jiang
authors.forename: Xianfa
authors.initials: X
authors.lastname: Tang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D012306:Risk; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D053759:Interleukin-23