title: The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes.
abstract: OBJECTIVE
  Cross-sectional studies suggest the association between diabetic nephropathy and the PPARγ2 Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 (PPARγ2). Prospective data are limited to microalbuminuria and no information on renal function is available to date. The present study evaluates the association between the Pro12Ala polymorphism of PPARγ2 and the progression of albuminuria and decay in glomerular filtration rate (GFR) in type 2 diabetes.
  
  
  METHODS
  We studied 256 patients with an average 5-year follow-up. Among others, urinary albumin excretion rate (UAER) was measured on spot sample, GFR was estimated with the CKD-EPI Equation.
  
  
  RESULTS
  Baseline UAER and GFR were similar for carriers or non-carriers of the polymorphism. At follow-up no significant changes from baseline were observed for UAER or eGFR in carriers of the Pro12Ala polymorphism whereas a significant increase in UAER [17 (11.3-37.9) versus 24.5 (13.8-49.9) μg/mg, p < 0.006)] and a significant reduction in the eGFR (82.8 ± 14.5 versus 80.3 ± 17.3 ml/min/1.73, m(2) p = 0.02), were observed in non carriers of the Pro12Ala polymorphism. Progression of nephropathy - defined according to a combined end point of UAER and eGFR- i.e. doubling of baseline UAER to at least 100 μg/mg, or new onset microalbuminuria, or progression from micro to macroalbuminuria, or 25% reduction of eGFR, or annualized eGFR decline >3 ml/min/year - was significantly less frequent in Ala carriers than non carriers (11.4% vs 35.8%; p < 0.01); HR adjusted for baseline age, AER, eGFR, HbA1c, diabetes duration and blood pressure was 0.32 (0.12-0.80).
  
  
  CONCLUSIONS
  This study found that among patients with type 2 diabetes, the PPARγ2 Pro12Ala polymorphism is protective against progression of nephropathy and decay of renal function independent of major confounders.
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Via S Pansini 5, Naples, 80131, Italy. emanuela1978@hotmail.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Lapice
authors.affiliation: Department of Cellular and Molecular Biology and Pathology A. Califano DBPCM, University of Naples Federico II, Via S Pansini 5, Naples, 80131, Italy. a.monticelli@ieos.cnr.it.|IEOS CNR, Via S Pansini 5, Naples, 80131, Italy. a.monticelli@ieos.cnr.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Monticelli
authors.affiliation: Department of Cellular and Molecular Biology and Pathology A. Califano DBPCM, University of Naples Federico II, Via S Pansini 5, Naples, 80131, Italy. cocozza@unina.it.
authors.forename: Sergio
authors.initials: S
authors.lastname: Cocozza
authors.affiliation: Department of Cellular and Molecular Biology and Pathology A. Califano DBPCM, University of Naples Federico II, Via S Pansini 5, Naples, 80131, Italy. michele.pinelli@gmail.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Pinelli
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Via S Pansini 5, Naples, 80131, Italy. sara18102003@yahoo.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Cocozza
authors.affiliation: Department of Public Health, University of Naples Federico II, Via S Pansini 5, Naples, 80131, Italy. dbruzzes@unina.it.
authors.forename: Dario
authors.initials: D
authors.lastname: Bruzzese
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Via S Pansini 5, Naples, 80131, Italy. riccardi@unina.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Riccardi
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Via S Pansini 5, Naples, 80131, Italy. ovaccaro@unina.it.
authors.forename: Olga
authors.initials: O
authors.lastname: Vaccaro
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D047495:PPAR gamma