IL23/Th17通路基因上位性作用与汉族人银屑病易感性研究

Genes in IL23/Th17 pathway have epistatic effects on psoriasis susceptibility in Chinese Han population

目的搜寻和鉴定银屑病发病过程中IL23/Th17信号通路基因上位性作用模型,为汉族人银屑病的发病机制、诊断和预测提供重要理论依据。方法通过文献复习法从IL23/Th17通路中选出与汉族人银屑病发病相关的11个基因,选取的11个基因在1139个银屑病病例和1694个对照样本中进行分型分析,通过多因子降维分析法(MDR)和Logistic Regres-sion algorithms等方法,找出IL23/Th17信号通路相关基因在银屑病发病中的上位性作用。结果发现1个三维基因交互作用[IL21,CCR4和TNF(χ2=5.02,P=0.025)]、3个二维基因交互作用[IL12RB1和CCR4(χ2=11.66,P=0.0201)、IL22和CCR4(χ2=11.97,P=0.0176)、IL12RB1和IL6(χ2=7.31,P=0.0069)]在银屑病的发病中起着重要作用。结论研究证实了IL23/Th17信号通路基因间的上位性作用在银屑病发病中起着重要作用。

Objective To investigate the gene-gene epistatic effects in IL23/Th17 pathway underlying psoriasis, and to provide important theoretical basis for the pathogenesis, diagnosis and prediction of psoriasis in Han population. Methods Through a review of the literature, 11 genes related with pathogenesis of psoriasis in Han population were selected from IL23/Th17 pathway. Single-nucleotide polymorphisms（SNPs） from 11 genes were genotyped in 1139 psoriatic patients and 1694 controls. Muhifactor dimensionality reduction（MDR） and logistic regression algorithms were applied to explore the gene-gene interactions. Results We found that there were a three-way interaction among IL21, CCR4 and TNF（x^2 = 5.02 ,P = 0. 025 ）and three pair-wise gene-gene interactions between IL12RB1 and CCR4 （x^2 = 11.66, P = 0. 0201 ）, IL22 and CCR4 （x^2 = 11.97, P = 0. 0176 ）, ILl2 RB 1 and IL6 （X^2 = 7.31, P = 0. 0069 ） in psoriasis. Conclusion Our results confirmed the importance of the epistatic effects of genes in the IL23/Th17 pathway for the pathogenesis of psoriasis.