MODY3基因在早发家族性2型糖尿病发病中的作用

The contribution of MODY3 gene to the pathogenesis of early onset familial type 2 diabetes in Chinese population

目的评估MODY3(HNF-1a)基因在中国家族性早发2型糖尿病(T2DM)发病中的作用。方法收集100个早发T2DM家系,PCR扩增先证者MODY3基因的外显子和外显子/内含子拼接区,产物直接测序。对发现的SNPs进行病例对照研究。结果发现5个非编码区DNA变异IVS1-16G>A、IVS2-23C>T、IVS5+9C>G、IVS7+7A>G、IVS9-24C>T,4个编码区的同义突变Leu17Leu、Gly288Gly、Thr515Thr、Leu459Leu,3个编码区的错义突变Pro379Ala、Ile27Leu、Ser487Asp,其中Pro379Ala突变在一个家系中与糖尿病共分离;Ile27Leu和Ser487Asp与糖尿病不相关。结论MODY3在中国早发家族性T2DM中患病率不超过1%,在中国家族性T2DM发病中不起主要作用。

Objective To evaluate the contribution of MODY3（HNF-1a） gene to pathogenesis of early onset familial type 2 diabetes in Chinese population. Methods 100 early onset type 2 diabetes pedigrees in Beijing were collected. By PCR, all the exons and exon/intron splice sites of MODY3 gene were amplified ,and PCR products were sequenced to identify the DNA variants. The identified SNPs were genotyped for case ontrol studies. Results We identified 5 DNA variants in noncoding region including IVS1-16G〉A, IVS2-23C〉T, IVS5＋9C〉G, IVS7＋7A〉G, and IVS9-24 C〉T; 4 silient mutations in coding region including Leu17Leu, Gly288Gly, Thr515Thr, and Leu459Leu and 3 misense mutations in coding region including Pro379Ala, Ile27Leu, and Ser487Asp. The Pro379A1a mutation was cosegregated with diabetes in a pedigree. We did not find the relationship of Ile27Leu and Ser487Asp with early onset familial type 2 diabetes. Conclusions Our research suggests in Chinese population the prevalences of MODY3 is not more than 1% in early onset familial type 2 diabetic patients. The MODY3 gene is impossible to take an important role in Chinese early onset familial type 2 diabetes.