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Impact of the Pro12Ala polymorphism of the PPAR-Gamma 2 gene on metabolic and clinical characteristics in the Palestinian type 2 diabetic patients.

ABSTRACT: Peroxisome proliferators activated receptor-gamma2 (PPAR?2) represents the transcriptional master regulator of adipocyte differentiation and therefore has been suggested as a candidate gene for obesity, insulin resistance, and dyslipidemia. The objective of the study was to investigate for the first time the potential association of the most common variant Pro12Ala (p.P12A) substitution of the PPAR?2 gene with body mass index (BMI), blood pressure, fasting plasma glucose, plasma total cholesterol, LDL and HDL cholesterol, and plasma triglyceride in a sample of 202 (138 females and 64 male) type 2 diabetic Palestinians. Genotyping of the PPAR?2 p.P12A polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The A12 allele was associated with lower fasting plasma glucose (P = .03) but had no influence on blood pressure, BMI, or other metabolic parameters. In obese patients, the p.P12A substitution was associated with elevated total plasma cholesterol levels (P = .02) and a tendency toward increased LDL cholesterol level (P = .06). In conclusion, the p.P12A variant of the PPAR?2 may influence cardiovascular risk through effects on lipid metabolism in obese T2D Palestinian patients.

SUBMITTER: Ereqat S

PROVIDER: S-EPMC2766506 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Impact of the Pro12Ala polymorphism of the PPAR-Gamma 2 gene on metabolic and clinical characteristics in the Palestinian type 2 diabetic patients.

Ereqat S S Nasereddin A A Azmi K K Abdeen Z Z Amin R R

PPAR research 20091025

Peroxisome proliferators activated receptor-gamma2 (PPARγ2) represents the transcriptional master regulator of adipocyte differentiation and therefore has been suggested as a candidate gene for obesity, insulin resistance, and dyslipidemia. The objective of the study was to investigate for the first time the potential association of the most common variant Pro12Ala (p.P12A) substitution of the PPARγ2 gene with body mass index (BMI), blood pressure, fasting plasma glucose, plasma total cholestero ...[more]

PMID: 19859551

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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

Impact of the Pro12Ala polymorphism of the PPAR-Gamma 2 gene on metabolic and clinical characteristics in the Palestinian type 2 diabetic patients.

Publications

Impact of the Pro12Ala polymorphism of the PPAR-Gamma 2 gene on metabolic and clinical characteristics in the Palestinian type 2 diabetic patients.

Similar Datasets

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