中国糖尿病人群TCF1基因突变的遗传及临床特征研究  

The genetic and clinical characteristics of transcription factor 1 gene mutations in Chinese diabetes

作　　者：杨震[1] 吴松华[1] 郑泰山[1] 王遂军[1] 陆惠娟[1] 项坤三[1] 

机构地区：[1]上海糖尿病研究所,上海交通大学附属第六人民医院内分泌代谢科,200233

出　　处：《中华医学遗传学杂志》2007年第2期157-161,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（30470813）;上海市科委重点项目基金（02DJ14052-1）

摘　　要：目的对中国早发及多发糖尿病患者进行转录因子1（transcription factor 1，TCF1，HNF-1A）基因筛查以了解中国人早发及多发糖尿病家系中TCF1基因突变发生情况及突变携带者临床特征。方法用PCR产物直接测序的方法在341个无亲缘关系的中国人[其中80名为正常对照者，261例为早发和（或）多发糖尿病家系先证者]中对TCF1基因启动子区，整个编码区及内含子／外显子结合区进行筛查。结果总共发现5个突变，其中4个突变位点（T82M，Q130H，G253G，P353fsdelACGGGCCTGGAGC）为新发现的突变位点，突变携带者平均体重指数为21．9kg／m^2，胰岛素分泌受损。本研究中TCF1基因突变在中国人早发性糖尿病患者中的发生率约为3％。此外，在261例先证者中还发现了11种碱基替换。其中有3种变异[IVS 1-8（G→A），IVS1-128（T→G）和IVS2＋21（G→A）]在80名非糖尿病健康对照中未被观察到，其中IVS 1-8（G→A）未见报道，且这两种在启动子处变异在家系中表现为与糖尿病共分离。结论TCFl基因突变不是中国人早发及多发糖尿病的主要原因。Objective To investigate the genetic and clinical features of mutations and sequence variations of the transcription factor 1 gene （TCF1,HNF-1A） in Chinese with familial early-onset and/or multiplex diabetes mellitus. Methods All ten exons of the TCF1 gene were screened, including exon/intron junctions, by direct sequencing method in 341 urtrelated Chinese subjects, including 80 healthy controls and 261 probands of early-onset and/or multiplex diabetes pedigrees. Results Five mutations were found in all. Four of the 5 different TCF1 mutations were newly identified novel mutations（T82M,Q130H, G253G,P353fsdelACGGGCCTGGAGC）, moan body mass index of mutation carriers was 21.9 kg/m^2, and insulin secretion was impaired in the mutation carriers. In this study, the maturity-onset diabetes of the young type Ⅲ （MODY3） only accounted for 3% of Chinese early-onset diabetes. Moreover, eleven substitutions were identified in261 probands. Of them, three variants [IVS1 -8 （G→A）, IVS1 - 128 （T→G）and IVS2 ＋ 21 （G→A）] were not observed in 80 healthy controls and one of them [ IVS1 -8（ G→A） ] was not reported previously and the two promoter variants co-segregated with diabetes. Conclusion TCF1 gene is not a common cause of early-onset and/or multiplex diabetes among Chinese patients.

关 键 词：糖尿病 转录因子1基因 直接测序 

分 类 号：R686[医药卫生—骨科学]