Association of Pro12Ala polymorphism of PPARgamma gene with insulin resistance and related diseases.

To clarify the contribution of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARgamma) gene to susceptibility to insulin resistance and related diseases, 505 unrelated Japanese subjects were investigated, including 175 normotensive non-diabetic (NN) subjects, 125 normotensive diabetic (ND) subjects, 102 hypertensive non-diabetic (HN) subjects, and 103 hypertensive diabetic (HD) subjects. Ala phenotype frequency was lowest in patients with both type 2 diabetes and hypertension (3.9% in HD group), followed by patients with either one of these conditions (5.6% in ND group, 7.8% in HN group), and highest in subjects without these conditions (9.7% in NN group). When stratified by hypertensive status, the Ala phenotype was negatively associated with diabetes, giving an odds ratio of 0.53 (95% confidence interval: 0.25-1.09). In contrast, when stratified by diabetic status, the odds ratio of the Ala phenotype for hypertension was 0.75 (95% confidence interval: 0.37-1.54). In non-diabetic hypertensive subjects, glucose and insulin levels during oral glucose tolerance test as well as M-value estimated by glucose-clamp test were not significantly different according to the genotype. The data suggest a contribution of the Pro12Ala polymorphism of PPARgamma to genetic susceptibility to type 2 diabetes mellitus and hypertension, but not to insulin sensitivity in hypertensive subjects.