TLR通路基因多态性与变应性鼻炎的关联研究  

Association of Toll-like receptor pathway gene polymorphisms with allergic rhinitis

作　　者：陈若希[1] 张清照[1] 陆美萍[1] 朱歆洁[1] 程雷[1,2,3] CHEN Ruoxi;ZHANG Qingzhao;LU Meiping;ZHU Xinjie;CHENG Lei(Department of Otorhinolaryngology,The First Affiliated Hospital,Nanjing Medical University,Nanjing 210029,Jiangsu,China;International Centre for Allergy Research,Nanjing Medical University,Nanjing 210029,Jiangsu,China;The Institute of Allergy and Autoimmune Disease,Jiangsu Clinical Medicine Research Institution,Nanjing 210029,Jiangsu,China)

机构地区：[1]南京医科大学第一附属医院江苏省人民医院耳鼻咽喉科,江苏南京210029 [2]南京医科大学国际变态反应研究中心,江苏南京210029 [3]江苏省临床医学研究院过敏与自身免疫性疾病研究所,江苏南京210029

出　　处：《山东大学耳鼻喉眼学报》2019年第3期79-87,共9页Journal of Otolaryngology and Ophthalmology of Shandong University

基　　金：江苏省“科教兴卫工程”医学重点学科(XK200719);医学重点人才(RC2007065,RC2011071)

摘　　要：目的 Toll样受体(TLR)信号通路一直是变应性鼻炎(AR)和哮喘等变态反应性疾病的研究热点,研究TLR通路基因单核苷酸多态性(SNPs)与AR发病的相关性及机制。方法采用基于医院的病例-对照研究,选择持续性AR患者452例及正常人群495例。通过生物信息学数据库系统筛选TLR通路基因6个SNPs,分别是TLR2的rs7656411、rs76112010、rs7682814,CD14的rs2563298、rs2569190、rs2569191。采用TaqMan技术对SNPs进行分型,ImmunoCAP100变应原体外检测系统测定血清总IgE、特异性IgE,分析SNPs与AR发病率的相关性,并探讨基因-基因相互作用。结果CD14的rs2563298、rs2569191基因分布在AR组与对照组比较有统计学意义(P<0.05)。TLR2的rs7656411和CD14的rs2563298、rs2569191在AR伴随哮喘组与正常对照组中基因分布有明显差异。此外TLR2的rs7656411在AR男性组和有家族史组与对照组的基因分布有明显差异,CD14的rs2563298、rs2569191在AR分组中与对照组均有明显差异。基因交互发现rs7656411,rs2563298、rs2569191三个位点存在阳性关联。结论TLR通路基因TLR2、CD14多态性与AR发病风险及其临床表型存在一定相关性。Objective The involvement of the Toll-like receptor(TLR)signaling pathway in allergic rhinitis(AR),asthma,and other allergic diseases is being intensively studied. The present study assessed the correlation between TLR pathway gene single nucleotide polymorphisms(SNPs)and incidence of AR,and investigated the influence of SNPs in the pathogenesis of AR. Methods Candidate TLR pathway SNPs were screened by a search of a bioinformatics database system using the TaqMan SNP genotyping system as part of a hospital-based case-control study of452 AR patients and491 healthy controls. Serum levels of eosinophil cationic protein,total IgE,and allergen-specific IgE were measured by the Immuno CAP blood test. Results Six SNPs were identified(TLR2 rs7656411,rs76112010,rs7682814 and CD14 rs2563298,rs2569190,rs2569191). Genotype frequencies of CD14 rs2563298 and rs2569191 were significantly different between the cases and controls(P<0.05). AR patients with asthma were significantly associated with the rs7656411,rs2563298,and rs2569191. Genotype frequencies of TLR2 rs7656411 were significantly different between controls and the male and history case subgroups. Significant differences were also found in genotypes of CD14 rs2563298 and rs2569191 compared with control and subgroups of cases. Gene interaction analysis revealed a three-locus interaction involving TLR2 rs7656411,CD14 rs2563298,and CD14 rs2569191 in AR cases. Conclusion Polymorphisms of TLR2 and CD14 in the TLR pathway may contribute to susceptibility of AR in this Chinese population.

关 键 词：变应性鼻炎 TOLL样受体 CD14 单核苷酸多态性 遗传学关联研究 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]