Longevity-associated mitochondrial DNA 5178 C/A polymorphism is associated with fasting plasma glucose levels and glucose tolerance in Japanese men

Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is reportedly associated with longevity in the Japanese population, and the Mt5178A genotype may resist the onset of type 2 diabetes. To investigate whether Mt5178 C/A polymorphism is associated with glucose tolerance, we conducted a cross-sectional study using the 75-g oral glucose tolerance test (OGTT) in which non-diabetic Japanese male subjects were classified into three subgroups by body mass index (BMI): BMI<22 (n=91); 22≤BMI<25 (n=138); and BMI≥25 (n=67). The frequency of Mt5178A was significantly lower among 'BMI<22' subjects exhibiting impaired fasting glucose and impaired glucose tolerance than among those with normal glucose tolerance. In the 'BMI<22' group, fasting plasma glucose (FPG) levels and plasma glucose levels at 60 and 120 min after glucose load (OGTT-1h and OGTT-2h, respectively) were significantly lower in the Mt5178A genotype than in the Mt5178C genotype. After adjusting for age, BMI, habitual smoking, habitual drinking and family history of diabetes, FPG levels and OGTT-2h levels were still significantly lower in the Mt5178A genotype than in the Mt5178C genotype. However, after adjusting for covariates, in both the '22≤BMI<25' and 'BMI≥25' groups, FPG levels were significantly higher in the Mt5178A genotype than in the Mt5178C genotype. Differences in the effect of alcohol consumption on FPG levels and glucose tolerance between the Mt5178 C/A genotypes were observed. The present results suggest that Mt5178 C/A polymorphism may be associated with FPG levels and glucose tolerance in middle-aged Japanese men.