TSHR基因上新发现SNP及其在GD致病中的评价  

A Novel Single Nucleotide Polymorphism of the Human Thyrotropin Receptor and Evaluation the Effect on Development of Graves Disease

作　　者：梁军[1] 高聆[2] 盛燕[3] 宋怀东[3] 赵家军[2] 

机构地区：[1]江苏省徐州市中心医院内分泌科,221009 [2]山东大学山东省立医院 [3]上海第二医科大学附属瑞金医院人类基因组国家重点实验室

出　　处：《医学研究杂志》2007年第5期30-33,共4页Journal of Medical Research

基　　金：国家自然科学基金资助项目(30470815);江苏省卫生厅资助项目(H200651);徐州市卫生局资助项目(XW2005017)

摘　　要：目的探讨TSH受体上单核苷酸多态性(SNP)与Graves病(GD)的相关性。方法(1)以一GD家系的12个成员(包括3例患者、9例家系成员)为研究对象,抽提外周血DNA,设计引物,扩增TSHR的全部外显子和部分内含子,PCR产物纯化后测序,对TSH受体的SNP进行筛查。(2)应用病例-对照研究方法,检测筛查出的SNP基因型和等位基因变化频率与GD有无相关性。结果共发现8个多态位点,其中第8外显子上的多态位点在SNP库中未见报道,为首次发现。这些多态位点的变化频率在患者与正常组间相比较,无明显统计学差异。结论新发现的SNP及其他多态位点与GD不连锁;提示汉族人TSH受体基因与GD无相关性;该基因的多态位点在不同的人种间存在明显差异。Objective To obtain more information concerning polymorphism of the thyrotropin （TSHR） in Graves diseases（GD）. Methods （1） A family of GD was studied （including 3 patients and 9 healthy family members） to examine SNPs of TSHR through direct sequencing of all 10 exons and part of introns. （2）In the current case -control study, 30 patients with familiar GD, 48 sporadic patients and 96 healthy control individuals were used to assess whether SNP of TSHR was associated with GD. Genomic DNA was extracted from peripheral leukocytes isolated from ACD -anticoagulated blood. Ten exons were amplified by PCR, using primers designed by ourselves. After purifying, the products were sequenced. Results Eight polymorphisms were found. There was a novel polymorphism in exon 8. There were no significant differences between patients and controls. Conclusions These findings suggested that the novel and other poly- morphisms of the TSHR gene may not be responsible for GD. There are racial differences in the distribution of polymorphisms of TSHR gene.

关 键 词：TSHR基因 单核苷酸多态性 GRAVES病 

分 类 号：R581.3[医药卫生—内分泌]