Meta-analysis of associations between the peroxisome proliferator-activated receptor-γ Pro12Ala polymorphism and susceptibility to nonalcoholic fatty liver disease, rheumatoid arthritis, and psoriatic arthritis

Genet Test Mol Biomarkers. 2014 May;18(5):341-8. doi: 10.1089/gtmb.2013.0503. Epub 2014 Apr 3.

Abstract

Introduction: The purpose of this study was to examine whether a Proline (Pro)-to-Alanine (Ala) exchange at codon 12 (Pro12Ala) polymorphism of the peroxisome proliferator-activated receptor-gamma (PPARγ) is associated with susceptibility to nonalcoholic fatty liver disease (NAFLD), rheumatoid arthritis (RA), and psoriatic arthritis (PsA).

Methods: A meta-analysis was conducted on the association between the PPARγ Pro12Ala polymorphism and NAFLD, RA, and PsA.

Results: Nine studies, including five on NAFLD, two on RA, and two on PsA, were available for the meta-analysis consisting of 8082 cases and 3790 controls. The meta-analysis revealed no association between the Ala allele of the PPARγ Pro12Ala polymorphism and NAFLD (odds ratios [OR]=0.936, 95% confidence interval [CI]=0.672-1.302, p=0.693). However, stratification by ethnicity indicated an association between the Ala allele and NAFLD in East Asians (OR=0.700, 95% CI=0.496-0.987, p=0.042), but not in Europeans (OR=1.128, 95% CI=0.863-1.475, p=0.378). Analysis using the dominant model showed the same Ala allele pattern in East Asians and Europeans (OR=0.688, 95% CI=0.484-0.978, p=0.037; OR=1.051, 95% CI=0.782-1.413, p=0.742), demonstrating a significant association between the Ala allele and NAFLD in East Asians. The meta-analysis revealed no association between the Ala allele and RA in East Asians (OR=0.467, 95% CI=0.188-1.161, p=0.101), and no association was found between the Ala allele and PsA in Europeans (OR=0.869, 95% CI=0.465-1.627, p=0.662).

Conclusions: Our meta-analysis demonstrates that the PPARγ Pro12Ala polymorphism is associated with susceptibility to NAFLD in East Asians, but not in European populations.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / genetics
  • Arthritis, Psoriatic / genetics*
  • Arthritis, Rheumatoid / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Non-alcoholic Fatty Liver Disease / genetics*
  • PPAR gamma / genetics*
  • Polymorphism, Genetic*
  • Proline / genetics

Substances

  • PPAR gamma
  • Proline
  • Alanine