The peroxisome poliferator-activated receptor-gamma 2 Pro12Ala variant - Association with type 2 diabetes and trait differences

Recent studies have identified a common proline-to-alanine substitution (Pr o12Ala) in the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamm a2), a nuclear receptor that regulates adipocyte differentiation and possib ly insulin sensitivity, The Pro12Ala variant has been associated in some st udies with diabetes-related traits and/or protection against type 2 diabete s. me examined this variant in 935 Finnish subjects, including 522 subjects with type 2 diabetes, 193 nondiabetic spouses, and 220 elderly nondiabetic control subjects, The frequency of the Pro12Ala variant was significantly lower in diabetic subjects than in nondiabetic subjects (0.15 vs, 0.21; P = 0.001), We also compared diabetes-related traits between subjects with and without the Pro12Ala variant within subgroups. Among diabetic subjects, th e variant was associated with greater weight gain after age 20 years (P = 0 .023) and lower triglyceride levels (P = 0.033), Diastolic blood pressure w as higher in grossly obese (BMI >40 kg/m(2)) diabetic subjects with the var iant. In nondiabetic spouses, the variant was associated with higher fastin g insulin (P = 0.033), systolic blood pressure (P = 0.021), and diastolic b lood pressure (P = 0.045). These findings support a role for the PPAR-gamma 2 Pro12Ala variant in the etiology of type 2 diabetes and the insulin resis tance syndrome.