TSHR基因内含子1区域单核苷酸多态性与Graves病的相关性研究  

The single nucleotide polymorphisms in the intron 1 of TSHR gene were associated with Graves＇ disease

作　　者：孙媛媛[1] 杜文华[2] 梁翠格[2] 刘晓萌[2] 李守杰[2] 李文侠[2] 董庆玉[2] 王月丽[2] 刘炳丽[3] 宋怀东[2] 高冠起[1] 

机构地区：[1]泰山医学院,泰安271016 [2]山东省临沂市人民医院 [3]上海交通大学附属瑞金医院分子医学中心、国家基因组学重点实验室

出　　处：《中华内分泌代谢杂志》2012年第7期565-569,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：基金项目：国家自然科学基金（30771017）;山东省自然科学举金（ZH2011HM067）

摘　　要：目的探讨中国山东临沂地区汉族人群促甲状腺素受体（TSHR）基因内含子1区域单核苷酸多态性（SNP）与Graves病的关系。方法应用全基因组关联研究（GWAS）和TaqMan探针技术，对1759例GD患者和1740名健康对照者TSHR内含子1区域进行基因分型：同时检测甲状腺激素水平及促甲状腺激素受体抗体（TRAb）水平。结果选取GWAS研究中发现的5个SNPs位点进入扩大样本的验证，发现rs12101261_T与GD关联性较强（OR=1．257，95％CI1．137～1．390，P=8．23×10^-6），logistic同归分析显示rs12101261是GD一个独立致病位点（P=1．61×10^-3）；rs12101261_T与治疗1年后TRAb阳性的患者显著相关（OR=1．317．95％CI1．171～1．481，P=4．14×10^-4），与TRAb阴性者无相关性（OR=1．056，95％C10．892～1．251，P=0．524）。rs12101261的3种基因型在TRAb阳性和阴性组的分布差异有统计学意义（P=0．014），其他临床表现差异均无统计学意义（P〉0．05）。结论TSHR基因内含子1区域5个SNP与山东临沂地区汉旅人群GD相关，其中rs12101261是一个独立致病位点．该基因多态性与血清TBAb水平相关。Objective To investigate the association between single nuclentide polymorphisms in the intron 1 of thyroid stimulating hormone receptor gene （TSHR） and Graves＇ disease （GD） in the Chinese Han population from Linyi city, Shandong Province. Methods A total of I 759 GD patients and 1 740 control subjects were recruited for genotyping in TSHR intron I with genome-wide assoeiation study （GWAS） and Taqman probe teehnique. At the same time, serum thyroid hormune and TSH receptor antibody （TRAb） levels of patients were determined. Results Five SN Ps were selected for further replication. The rsl 2101261 T was significantly associated with GD risk （ OR = 1. 257, 95% CI 1. 137-1. 390, P = 8.23 × 10^-6）. Logistic regression identified that rsl210126l was an independent sasceplihilily loeas of GD （ P= 1. 61 × 10-3 ）. Furthermore, rs12101261 _T was struugly associated with GD （ OR = 1. 317, 95% CI 1. 171-[. 481, P = 4.14 × 10-4） in TRAb positive patients, hut no association in TRAb negative patients （ OR = 1,056,95 % CI O. 892-1.251 , P = 0. 524 ）. Serum TRAb cuueentration showed remarkable difference among three genolype groups of rs12101261. Conclusions Five SNPs in TSltR intron 1 are associated with GD. rsl 2101261 contributes to increased GD risk independently and is associated with serum TRAb level.

关 键 词：格雷夫斯病 促甲状腺素受体 内含子 多态性 单核苷酸 促甲状腺激素受体抗体 

分 类 号：R581.1[医药卫生—内分泌]