线粒体基因突变与NIDDM发生的关系  

Mitochondrial DNA Mutation Associated with NIDDM

作　　者：周晓雷[1,2] 张丽珊[1,2] 黄鹰[1,2] 田成功[1,2] 邱定红[1,2] 陆明华[1,2] 张志平[1,2] 

机构地区：[1]南京铁道医学院生物学教研室 [2]南京市鼓楼医院内分泌科

出　　处：《遗传》1997年第2期5-8,共4页Hereditas（Beijing)

摘　　要：采用ＰＣＲ－ＳＳＣＰ、ＰＣＲ－ＲＦＬＰ及ＰＣＲ产物直接测序等技术对９０例ＮＩＤＤＭ（即非胰岛素依赖型糖尿病）及８０例正常对照个体的血细胞线粒体ＤＮＡ进行了突变分析。结果在２例患者中发现线粒体ＤＮＡ（ｍｉｔｏｃｈｏｎｄｒｉａｌＤＮＡ，ｍｔＤＮＡ）ＮＤ１（ＮａＤＨＤｅｈｙｄｒｏｇｅｎａｓｅｓｕｂｕｎｉｔＩ）基因上３３１６位点存在Ｇ→Ａ的点突变，导致丙氨酸错义突变成苏氨酸，而在８０例正常对照个体中均不存在此位点突变。国内外已证实的和１５％ＮＩＤＤＭ发生有关的ｍｔＤＮＡｔＲＮＡＬｅｕ［（ＵＵＲ）］基因上３２４３位点Ａ→Ｇ的突变在本实验中并未发现。由此推断，３３１６位点Ｇ→Ａ的突变可能与ＮＩＤＤＭ的发生有关，３２４３位点Ａ→Ｇ的突变率确实很低，可见糖尿病的发生在线粒体遗传上具有广泛的异质性。Using PCR-SSCP, PCR-RFLP and PCR product direct sequencing techniques, we analysed the mitochondrial DNAs (mtDNAs) of 90 patients with NIDDM (Non Insulin-Dependent Diabetes Mellitus) and those of 80 normal controls. The results showed that a G to A mutation which leads alanine's missence mutaton to threonine in the mitochondrial ND1(NaDH Dehydrogenase subunit I gene at nucleotide pair 3 316 occurred in the blood cells of 2 patients. We have not however, indentified with the A to G mutation at nucleotide pair 3 243 of the mitochondrial tRNA Leu gene, which has been reported to associate with NIDDM in about 1.5% of the diabetic population. We infer that the mutation at position 3316 is perhaps associated with the development of NIDDM, the occurance of the mutation at position 3243 is actually rare, and NIDDM has an intensive mitochondrial genetic heterogenous background.

关 键 词：非胰岛素依赖型糖尿病 线粒体DNA 错义突变 

分 类 号：R587.102[医药卫生—内分泌]