The Human Peroxisome Proliferator-Activated Receptor γ2 (PPARγ2) Pro12Ala Polymorphism is Associated with Decreased Risk of Diabetic Nephropathy in Patients with Type 2 Diabetes

The peroxisome proliferator-activated receptor γ2 (PPARγ2) Pro12Ala polymorphism has been associated with a decreased risk of type 2 diabetes and a lower albumin excretion rate (AER) in patients with established diabetes. We performed a case-control study aiming to evaluate the association between the Pro12Ala polymorphism and diabetic nephropathy. Genomic DNA was obtained from 104 type 2 diabetic patients (case subjects) with chronic renal insufficiency (78 on dialysis and 26 with proteinuria [AER ≥200 μg/min] and serum creatinine ≥2.0 mg/dl) and 212 normoalbuminuric patients (AER <20 μg/min) with known diabetes duration ≥10 years (control subjects). The genotypic distribution of the PPARγ2 Pro12Ala polymorphism in these diabetic patients was in Hardy-Weinberg equilibrium, and the Ala allele frequency was 9%. The frequency of Ala carriers (Ala/Ala or Ala/Pro) was 20.3% in control subjects and 10.6% in case subjects (P = 0.031). The odds ratio of having diabetic nephropathy for Ala carriers was 0.465 (95% CI 0.229-0.945; P = 0.034). Carriers of the Ala allele were not different from noncarriers (Pro/Pro) regarding sex (38.9 vs. 44.1% males) or ethnicity (77.4 vs. 71.7% white) distribution, age (61 ± 10 vs. 61 ± 10 years), known diabetes duration (17 ± 7 vs. 16 ± 7 years), BMI (27 ± 4 vs. 28 ± 5 kg/m²), fasting plasma glucose (184 ± 81 vs. 176 ± 72 mg/dl), HbA_1c (6.7 ± 2.3 vs. 6.9 ± 2.4%; high-performance liquid chromatography reference range: 2.7-4.3%), and systolic (145 ± 27 vs. 0.144 ± 24 mmHg) or diastolic (87 ± 14 vs. 85 ± 14 mmHg) blood pressure, respectively. In conclusion, the presence of the Ala allele may confer protection from diabetic nephropathy in patients with type 2 diabetes.