Mitochondrial gene mutations and type 2 diabetes in Chinese families / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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)).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Study on the mitochondrial DNA mutations in patients with early-onset diabetes mellitus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of mitochondrial DNA (mtDNA) mutations in patients with early-onset diabetes in Tianjin, and to explore the relationship between mtDNA mutations and diabetes.</p><p><b>METHODS</b>348 non-related patients whose age at onset of diabetes was less than 45 years were randomly recruited, and 207 non-related and non-diabetic subjects were enrolled as controls. All their clinical and biochemical data were collected. Total genome was extracted conventionally from the participants' peripheral leucocytes, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and cloning techniques were applied to the screening of mtDNA mutations (including the 3316, 3394 and 3426 in ND1 region, 12026 in ND4 region, and tRNA [Leu(UUR)] 3243 A-->G mutation).</p><p><b>RESULTS</b>The authors found 17 diabetics harboring the 12026 A-->G mutation in ND4 region (4.9%), 10 diabetics with mutations in ND1 region (including 5 diabetics with the 3394 T-->C mutation, 4 diabetics with 3316 G-->A mutation, one with 3426 A-->G mutation), and only two with the known 3243 A-->G mutation (0.6%). On the contrary, one control subject with the 3316 G-->A mutation, two with 3394 T-->C mutation and four with 12026 A-->G mutation were found. The prevalence of mtDNA mutations in the patient group is significantly higher than that in the control group (3.3%) (P<0.05).</p><p><b>CONCLUSION</b>The above findings suggest that mtDNA mutation may be implicated in the pathogenesis of the examined diabetes.</p>

Relationship between mutations of mitochondrial DNA ND1 gene and type 2 diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Study on a new point mutation of nt3426 A --> G of mitochondrial DNA in a diabetes mellitus family / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To elucidate the relationship between point mutations of nt3243A --> G, nt3426 A --> G of mitochondrial DNA and type 2 diabetes mellitus(DM).</p><p><b>METHODS</b>Two hundred patients with type 2 DM and 180 controls with normal glucose tolerance and absence of DM family history were included. The mutations were determined by PCR-restriction fragment length polymorphism.</p><p><b>RESULTS</b>The point mutation nt3426A --> G of mitochondrial DNA ND1 was found in 2 of the patients with type 2 DM (1.0%) but in none of the controls (0). The incidence of this mutation showed no significant difference between the two groups(P>0.05). And none was found to have the mutation of nt3243 --> G.</p><p><b>CONCLUSION</b>The point mutation nt3426 A --> G of mitochondrial DNA ND1 may not be an independent factor to cause type 2 DM.</p>