江苏镇江地区早发糖尿病家系HNF1α基因突变筛查.docVIP

江苏镇江地区早发糖尿病家系HNF1α基因突变筛查 　 作者：王莹，陈军建, 王东, 范昕, 俞力 【摘要】 　　目的： 探讨江苏镇江地区家族性早发糖尿病与年轻起病成人型糖尿病(maturityonset diabetes of the young, MODY)基因(HNF1α)多态性的关系。方法： 收集80个早发糖尿病家系，另选96例非糖尿病者为对照。提取研究对象血DNA，用PCR产物扩增HNF1α基因的所有外显子，将PCR产物直接进行测序，对HNF1α基因多态性进行筛查。结果： 在80例糖尿病家系先证者中筛查到两个编码区的变异：位于1号外显子的Ile27Leu及7号外显子的Leu459Leu变异。Ile27Leu错义突变的基因型和等位基因频率在糖尿病先证者和正常对照者中无显著差别(Pgt;0.05)。Leu459Leu同义突变仅在1例先证者中被发现，在该家系中与糖尿病共分离。该突变在正常者中未查到。结论： HNF1α基因突变在江苏镇江地区早发家族性2型糖尿病中不起主要作用。 【关键词】 早发糖尿病；青年发病的成人糖尿病； 突变 　　［Abstract］Objective: To investigate the prevalence of mutations of hepatocyte nuclear factor(HNF)1α gene in Jiangsu Zhenjiang families with earlyonset diabetes mellitus. Methods： Eighty pedigrees probands of earlyonset diabetes were collected in Jiangsu Zhenjiang area， who were diagnosed as type 2 diabetes under 40 years old and， at least， another first relatives was diagnosed as type 2 diabetes under 45 years old. Another 96 nondiabetic subjects were enrolled as controls. By PCR， all the exons of MODY3 gene were amplified and PCR products were sequenced to identify the DNA variants. Results： By screening MODY3 gene in 80 diabetic probands， two DNA variants were identified in coding region， including which we found one Ile27Leu missense mutations in exon 1 and one Leu459Leu samesense mutation in exon 7. There were no difference between the Chinese familial earlyonset diabetes mellitus and the normal controls in polymorphism allelic frequency and genotype frequency of the Ile27Leu mutation(Pgt;0.05). The Leu459Leu samesense mutation was only found in one proband. It was cosegregated in the pedigree′s members and was not found in normal control subjects. Conclusion： No enough evidence demonstrates that the variation in HNF1α gene is the major cause of earlyonset diabetes in Jiangsu Zhenjiang population. 　　［Key words］type 2 diabetes; MODY; mutation 年轻的成人发病型糖尿病(maturityonset diabetes of the young, MODY) 是一组单基因突变所致特殊类型糖尿病。 目前发现至少6种基因突变可致病，其中HNF1α（MODY3 ）是最常见的一种。由于种族、地