Antiatherogenic mitochondrial genotype in patients with type 2 diabetes

OBJECTIVE - To evaluate the significance of a longevity-associated mitochon drial genotype (Mt5178A) derived from a C --> A transversion at nucleotide position 5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH dehydrogonase subunit 2 gene, in type 2 diabetic subjects. RESEARCH DESIGN AND METHOD- Mt5178 typing was done by polymerase chain reac tion-restriction fragmennt-length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic Japanese subjects, and the results were compa red with the clinical characteristics. Then, the association of Mt5178 type with early atherosclerotic changes of the bilateral carotid arteries on ul trasonography was assessed in 412 diabetic subjects randomly selected from the original 1,148 type 2 diabetic subjects, while maintaining the same fre quency of Mt5178A and Mt5178C. RESULTS - The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was not different from that previously found in health blood do nors (114 of 252; 45%). Clinical characteristics regarding diabetes were no t significantly different between the Mt5178A group (n = 454) and the Mt517 8C group (n = 694). However, the mean intima-media thickness (IMT) at six s ites in the bilateral carotid arteries was significantly smaller in the Mt5 178A group than in the Mt5178C group (0.906 +/- 0.018 vs. 0.995 +/- 0.021 m m, mean +/- SEM, P = 0.022), and the Mt5178 type was significantly correlat ed with both the mean IMT and the presence of plaque on multiple regression analysis and discriminant analysis. CONCLUSIONS - The Mt5178A genotype may be unrelated to the etiology of type 2 diabetes. However, Mt5178A seems to have an antiatherogenic effect, at l east in type 2 diabetic individuals.