线粒体DNA ND1基因变异与2型糖尿病的关系

Relationship between mutations of mitochondrial DNA ND1 gene and type 2 diabetes.

作者信息

Yu Pei, Yu De-min, Liu De-min, Wang Kun, Tang Xin-zhi

机构信息

Metabolic Disease Hospital, Tianjin Medical University, 300070, China.

出版信息

Chin Med J (Engl). 2004 Jul;117(7):985-9.

PMID:15265369

Abstract

BACKGROUND

Recent studies have indicated that many mutations in mitochondrial (mt) DNA NDI gene region are related to diabetes mellitus. In this study we explored the relationship between various mtDNA ND1 gene mutations and type 2 diabetes mellitus (DM) among Chinese.

METHODS

Using PCR restriction fragment length polymorphism (PCR-RFLP) analysis and gene sequencing, 4 spots of mtDNA (nt3243, nt3316, nt3394, nt3426) were screened in 478 diabetics and 430 non-diabetic subjects.

RESULTS

In diabetic group, there were 13 carriers (2.72%) of 3316 G-->A mutation,12 (2.51%) of 3394 T-->C mutation and 2 (0.42%) of 3426A-->G mutation. In controls, only 3394 T-->C mutation was observed in 2 subjects (0.47%). There was significant difference in the frequency of 3316 and 3394 mutation between two groups (P < 0.05, respectively). More subjects with mitochondrial DNA ND1 gene mutations had DM family history and greater tendency of maternal inheritance when compared to those patients without mutation in diabetic group (P < 0.01). A 3426 mutation diabetic pedigree was studied, and we found 12 maternal members in the family had the same mutation.

CONCLUSION

mtDNA ND1 gene mutations at nt3316 (G-->A), nt3394 (T-->C) and 3426 (A-->G) might contribute to the pathogenesis of DM with other genetic factors and environment factors.

摘要

背景

近期研究表明，线粒体（mt）DNA ND1基因区域的许多突变与糖尿病有关。在本研究中，我们探讨了中国人群中各种mtDNA ND1基因突变与2型糖尿病（DM）之间的关系。

方法

采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析和基因测序，对478例糖尿病患者和430例非糖尿病受试者的mtDNA的4个位点（nt3243、nt3316、nt3394、nt3426）进行筛查。

结果

糖尿病组中，3316 G→A突变携带者有13例（2.72%），3394 T→C突变携带者有12例（2.51%），3426 A→G突变携带者有2例（0.42%）。对照组中，仅在2例受试者（0.47%）中观察到3394 T→C突变。两组间3316和3394突变频率存在显著差异（P均<0.05）。与糖尿病组中无突变的患者相比，更多有线粒体DNA ND1基因突变的受试者有糖尿病家族史，且有更大的母系遗传倾向（P<0.01）。对一个3426突变的糖尿病家系进行研究，发现该家族中有12名母系成员有相同突变。