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The PPAR?2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes.

ABSTRACT: Cross-sectional studies suggest the association between diabetic nephropathy and the PPAR?2 Pro12Ala polymorphism of the peroxisome proliferator-activated receptor ?2 (PPAR?2). 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 PPAR?2 and the progression of albuminuria and decay in glomerular filtration rate (GFR) in type 2 diabetes.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.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) ?g/mg, p?3 ml/min/year - was significantly less frequent in Ala carriers than non carriers (11.4% vs 35.8%; p?

SUBMITTER: Lapice E

PROVIDER: S-EPMC4358785 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes.

Lapice Emanuela E Monticelli Antonella A Cocozza Sergio S Pinelli Michele M Cocozza Sara S Bruzzese Dario D Riccardi Gabriele G Vaccaro Olga O

Journal of translational medicine 20150312

<h4>Objective</h4>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.<h4>Patie ...[more]

PMID: 25889595

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Project description:OBJECTIVE: Cross-sectional studies found less microalbuminuria in type 2 diabetic patients with the Ala12 allele of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) Pro12Ala polymorphism. We prospectively evaluated the association between Pro12Ala polymorphism (rs1801282) and new-onset microalbuminuria. RESEARCH DESIGN AND METHODS: Pro12Ala polymorphism was genotyped by TaqMan-based assay in genomic DNA of 1,119 consenting patients from BErgamo NEphrologic DIabetic Complications Trial (BENEDICT)-a prospective, randomized trial evaluating ACE inhibition effect on new-onset microalbuminuria (albuminuria 20-200 microg/min in at least two of three consecutive overnight urine collections in two consecutive visits) in hypertensive type 2 diabetes with albuminuria <20 microg/min at inclusion. RESULTS: Baseline characteristics of Ala (Ala/Ala or Ala/Pro) carriers and Pro/Pro homozygotes were similar, with a nonsignificant trend to lower albuminuria (P = 0.1107) in the 177 Ala carriers. Over a median (interquartile range) of 44.0 (17.1-51.9) months, 7 (4%) Ala carriers and 86 (9.1%) Pro/Pro homozygotes developed microalbuminuria (hazard ratio [HR] 0.45 [95% CI 0.21-0.97]; P = 0.042). Final albuminuria was significantly lower in Ala carriers than Pro/Pro homozygotes (7.3 +/- 9.1 vs. 10.5 +/- 24.9 microg/min, respectively), even after adjustment for baseline albuminuria (P = 0.048). Baseline and follow-up blood pressure and metabolic control were similar in both groups. Incidence of microalbuminuria was significantly decreased by ACE versus non-ACE inhibitor therapy in Pro/Pro homozygotes (6.3 vs. 11.9%, respectively, HR 0.46 [0.29-0.72]; P < 0.001). CONCLUSIONS: In type 2 diabetes, the Ala allele protects from worsening albuminuria and new-onset microalbuminuria, and ACE inhibition blunts the excess risk of microalbuminuria associated with the Pro/Pro genotype. Evaluating Pro12Ala polymorphism may help identifying patients at risk who may benefit the most from early renoprotective therapy.

Dataset Information

The PPAR?2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes.

Publications

The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes.

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