Mitochondrial gene mutations and type 2 diabetes in Chinese families.

BACKGROUND: Numerous mitochondrial DNA mutations are significantly correlated with development of diabetes. This study investigated mitochondrial gene, point mutations in patients with type 2 diabetes and their families. METHODS: Unrelated patients with type 2 diabetes (n = 826) were randomly recruited; unrelated and nondiabetic subjects (n = 637) served as controls. The clinical and biochemical data of the participants were collected. Total genome was extracted from peripheral leucocytes. Polymerase chain reaction, restriction fragment length polymorphism (PCR-RFLP) and cloning techniques were used to screen mitochondrial genes including np3316, np3394 and np3426 in the ND1 region and np3243 in the tRNA(Leu(UUR)). RESULTS: In 39 diabetics with one or more mitochondrial gene point mutations, the prevalence (4.7%, 39/826) of mtDNA mutations was higher than that (0.7%, 5/637) in the controls. The identical mutation was found in 23 of 43 tested members from three pedigrees. Affected family members presented with variable clinical features ranging from normal glucose tolerance to impaired glucose tolerance (IGT) (n = 2), impaired fasting glucose (IFG) (n = 1) to type 2 diabetes (n = 13) with 3 family members suffering from hearing loss. CONCLUSIONS: Type 2 diabetes in China is associated with several mitochondrial gene mutations. Aged patients with diabetic family history had a higher prevalence of mutation and various clinical pictures. Mitochondrial gene mutation might be one of the genetic factors contributing to diabetic familial clustering.

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

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.