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Diabetes 51:2653-2657, 2002
© 2002 by the American Diabetes Association, Inc.
Peroxisome Proliferator-Activated Receptor-
2 Polymorphism Pro12Ala Is Associated With Nephropathy in Type 2 Diabetes
The Berlin Diabetes Mellitus (BeDiaM) Study
1 Department of Clinical Pharmacology, Division of Endocrinology and Nephrology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany
2 Department of Internal Medicine, Division of Endocrinology and Nephrology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany
3 Study Coordinating Centre, Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven, Leuven, Belgium
The Pro12Ala polymorphism of the gene encoding the peroxisome proliferator-activated receptor (PPAR)-
2 has recently been shown to be associated with type 2 diabetes. In the present analysis, we investigated whether PPAR-2 Pro12Ala was associated with microvascular complications of type 2 diabetes, such as albuminuria, end-stage renal failure (ESRF), or retinopathy. A total of 445 patients with type 2 diabetes who were enrolled in the Berlin Diabetes Mellitus Study and in whom we determined albuminuria and the presence of ESRF and retinopathy were genotyped for the PPAR-2 Pro12Ala polymorphism. We also measured potentially important covariables, such as blood pressure, BMI, duration of diabetes, glycosylated hemoglobin, serum creatinine, and serum lipids. Among 445 patients with type 2 diabetes (mean age 59.3 years), the Pro12Ala genotype distribution was in Hardy-Weinberg equilibrium (P = 0.42). The Ala12 allele frequency was 0.14. With adjustment for covariables, the 118 Ala12 allele carriers had significantly lower urinary albumin excretion (UAE) than the 327 noncarriers (17.1 vs. 25.8 mg/d; P = 0.01). The percentage decrease in UAE observed in PPAR- Ala12 allele carriers relative to noncarriers (P = 0.003) rose from 0.2% (P = 0.99) to 54% (P = 0.008) and to 70% (P = 0.01) when the duration of diabetes increased from <10 years to 10–19 years and to 
20 years, respectively. Similarly, the odds ratios of having albuminuria decreased from 1.22 (P = 0.54) to 0.61 (P = 0.23) and to 0.11 (P = 0.007), respectively. Among patients with type 2 diabetes, PPAR-2 Ala12 allele carriers had significantly lower UAE and tended to develop overt proteinuria less frequently. These observations suggest a protective effect of the Ala12 allele in relation to diabetic nephropathy.
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