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.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
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）
关键词
糖尿病
转录因子1基因
直接测序
diabetes
transcription factor 1 gene
direct sequencing
作者简介
通信作者：吴松华，Email：yangzhen1020@hotmail．com
