Association between the Interaction of Key Genes Involved in Effector T-Cell Pathways and Susceptibility to Develop allergic Rhinitis: A Population-Based Case-Control Association Study.
Association between the Interaction of Key Genes Involved in Effector T-Cell Pathways and Susceptibility to Develop allergic Rhinitis: A Population-Based Case-Control Association Study.
复制标题
效应 T 细胞通路中涉及的关键基因的相互作用与过敏性鼻炎易感性之间的关联：一项基于人群的病例对照关联研究。
DOI：
10.1371/journal.pone.0131248
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Zhang Y;Li J;Wang C;Zhang L
有证据表明，介导信号传导的关键基因和涉及效应T细胞应答的转录网络之间的相互作用可能会影响个体对过敏性鼻炎（AR）的易感性。本研究的目的是确定在中国汉族受试者中，参与效应T细胞通路的关键基因之间的特异性相互作用是否与个体发生AR的易感性相关。从中国北京的汉族人群中招募了489例AR患者和421例健康对照者。通过问卷调查和临床检查确定AR，并抽取所有受试者的外周血提取DNA。从北京地区汉族人群国际单倍型作图数据库中筛选出26个与辅助性T细胞1型（Th 1）、Th 2、Th 17、Th 9和调节性T细胞通路相关的候选基因，共96个单核苷酸多态性（SNP），采用IlluminaGoldenGate法进行SNP分型。使用PLINK软件包进行统计分析。单核苷酸多态性与表型的关联分析显示IL-17 A基因rs 8193036、IL-12基因rs 2569254和RORα基因rs 1898413与AR显著相关。rs 8193036为IL-17 A等位基因，rs 897200为STAT 4基因型，rs 1898413为RORα基因型。上位性分析显示，23个基因中的83个SNP具有显著的交互作用，其中59个交互作用/SNP对的OR值大于2或小于0.5，12个交互作用/SNP对的OR值大于4或小于0.25。参与Th 17通路的STAT 3、RORα和IL-26是最常见的相互作用基因。这项研究表明，参与效应T细胞途径的关键基因中的几个SNP之间的相互作用可能会影响个体对AR的易感性。
Evidence suggests that interaction between key genes mediating signaling and transcriptional networks involving effector T-cell responses may influence an individual’s susceptibility to develop allergic rhinitis(AR). The aim of this study was todetermine whether specific interactions between key genes involved in effector T-cell pathways are associated with an individual’s susceptibility to develop AR in Han Chinese subjects. A cohort of 489 patients with AR and 421 healthy controls was enrolled from the Han Chinese population in Beijing, China. AR was established by questionnaire and clinical examination, and peripheral blood was drawn from all subjects for DNA extraction. A total of 96 single nucleotide polymorphisms (SNPs) in 26 reprehensive candidate genes involved in T helper 1 (Th1), Th2, Th17, Th9 and T regulatory cell pathways were selected from the International Haplotype Mappingdatabase for Han Chinese in Beijing (CHB) population, and IlluminaGoldenGate assay was conducted for SNP genotyping. The PLINK software package was used to perform statistical analyses. Simple SNP-phenotype association analysis using logistic regression showed SNP rs8193036 in IL17A gene, rs2569254 in IL-12 and rs1898413 in RORα weresignificantlyassociatedwith AR.Simple SNP-phenotype association analysis with genetic models demonstrated thatrs2569254 in IL-12, rs1031508 in STAT4, and rs3741809 in IL-26 were likely to be recessive, rs8193036 in IL17A allelic, rs897200in STAT4 genotypic, and rs1898413 in RORα dominant. Epistasis analyses exhibited that 83 SNPs in 23 genes were significantly interactive; of which 59 interactions/SNP pairs demonstrated OR values higher than 2 or lower than 0.5, and 12 interactions/SNP pairs OR values higher than 4 or lower than 0.25. STAT3, RORα and IL-26, involved in Th17 pathway,were the mostfrequentlyinteractive genes. This study suggests that interactions between several SNPs in key genes involved in effector T-cell pathways are likely to influence an individual’s susceptibility to develop AR.