线粒体基因nP3316G→A突变与糖尿病

Point mutation np33l6G→A of mitochondrial DNA and diabetes mellitus

目的了解线粒体NADH俄氢酶亚单位1（ND1）基因中的3316位点G→A突变在我国DM患者中的存在情况。方法对随机收集的无血缘关系的262例2型DM、107例1型DM患者进行了研究，同时选择122例无糖尿病家族史的精耐量正常者作为对照。用聚合酶键反应扩增、限制性内切酶MscI消化进行点突变筛选。结果突变在2型DM中占1．9％（5／262），1型DM中占3．6％（4／09）。在GAD抗体阳性的1型DM中占8．5％（4／47），而122例非糖尿病患者未检出该突变（P＜0．01）。结论ND1基因3316G→A突变可能是一种2型DM和GAD抗体阳性的1型DM易感基因之一，突变的1型DM患者同时携带HLA－DQ易感基因，提示1型DM患者可同时有2种以上的遗传易感因素。

<Abetract>Objective Recently np3316G→A mutation of MtDNA NADH dehydrogenase subunit I (ND1) gene was also found to be one of the susceptible genes in type 2 DM. In order to understand the prevalence and the genetic and clinical pro files of the very mutation in Chinese with type 2 DM and type 1 DM, the following study was conducted.Methods 262 cases with type 2 DM, 47 cases with type 1 DM with positive glutamic decarboxylase antibody and 122 subjects with normal glucose tolerance (NGT) and also without DM family history were included. The mutation was determined by PCR-RFLP. Briefly, the target fragments were amplified by polmperase chain reaction (PCR), PCR products were digested with restricted endonuclease MscI, and mitochondrial ND1 gene mutations were confirmed by electrophoresis of digestion products with 1. 5% agarose. Results ND1 gene mutation was found in 5 of 262 patients with type 2 DM (1. 9% ), 4 of 47 type 1 DM (8. 5 % ) but none of 122 NGT contr0ls (0% ). Conclusion Point mutation np3316G→A of ND1 may be one of susceptible genes for type 2 DM and type 1 DM with positive Ab of GAD. There was susceptible HLA-DQ gene in every type 1 DM patients with ND1 mutation. It suggested that there may be more than 2 susceptible hereditory factors.