Association of the mitochondrial DNA 5178A/C polymorphism with maternal inheritance and onset of type 2 diabetes in Japanese patients.

The mitochondrial DNA 5178A/C (mt5178A/C) polymorphism is associated with longevity and adult onset diseases. We investigated an association of the mt5178A/C polymorphism with the occurrence and clinical features of type 2 diabetes. Two hundred and seventy Japanese patients with type 2 diabetes (181 men and 89 women) and 254 control subjects without diabetes were studied. Patients with mutations at position 3243 in the mitochondrial DNA were excluded. Genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism method. Various clinical features including age at disease onset were compared between the patients with the mt5178A and mt5178C alleles. Mt5178C was observed more frequently in patients with type 2 diabetes than in control subjects (65.9% vs 57.9%, P = 0.058). Clear information about the maternal history of diabetes was obtained from 233 diabetic patients. Patients with a maternal history of diabetes carried the mt5178C allele (58/75, 77.3%) more frequently than did patients without a maternal history of diabetes (100/158, 63.3%; P = 0.032) and control subjects (57.9%; P = 0.002). The mean age at onset of diabetes was significantly lower in patients with mt5178C (47.6 +/- 11.4 years) than in patients with mt5178A (51.5 +/- 10.0 years; P = 0.0073). The mt5178A/C polymorphism may be associated with maternal inheritance of type 2 diabetes and may influence the age at onset through deterioration of mitochondrial function.