Peroxisome proliferator-activated receptor-gamma2 polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: The Berlin Diabetes Mellitus (BeDiaM) Study.
The Pro12Ala polymorphism of the gene encoding the peroxisome proliferator-activated receptor (PPAR)-gamma2 has recently been shown to be associated with type 2 diabetes. In the present analysis, we investigated whether PPAR-gamma2 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-gamma2 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-gamma 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 >or=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-gamma2 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.
Herrmann
Stefan-Martin
SM
Department of Clinical Pharmacology, Division of Endocrinology and Nephrology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany.
Ringel
Jens
J
Wang
Ji-Guang
JG
Staessen
Jan A
JA
Brand
Eva
E
D000409:Alanine; D019943:Amino Acid Substitution; D015992:Body Mass Index; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics; D005260:Female; D005838:Genotype; D005858:Germany; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D011392:Proline; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics
D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D011392:Proline; D000409:Alanine