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PPARG gene Pro12Ala variant contributes to the development of non-alcoholic fatty liver in middle-aged and older Chinese population

Author

  • Zhen Yang
  • Jie Wen
  • Qin Li
  • Xiaoming Tao
  • Zi Ye
  • Min He
  • Weiwei Zhang
  • Ying Huang
  • Lili Chen
  • Charlotte Ling
  • Shen Qu
  • Renming Hu

Summary, in English

Oxidative stress has been suggested to contribute to the development of non-alcoholic fatty liver disease (NAFLD). Peroxisome proliferator-activated receptor gamma (PPAR-gamma) heterozygous mice and Pro12Ala (C/G) polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which could accelerates oxidative stress under overnutrition. To explore whether the C/G polymorphism, alone or in combination with smoking, may promote the development of non-alcoholic fatty liver, a case-control study was performed in 903 Chinese subjects. Among the study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with steatosis hepatis I degrees, 90 with steatosis hepatis II degrees and 28 with steatosis hepatis III degrees) and 467 controls were genotyped by using TaqMan allelic discrimination assays. After adjusting for confounders, the C/C genotype significantly associated with NAFLD (OR = 1.87, 95%CI 1.13-2.85, p = 0.009); smoking was also an independent risk factor for NAFLD (OR = 1.69, 95%CI 1.18-2.43, p = 0.025). In addition, we found possible synergistic effects, the higher risk group (smokers with the C/C genotype) showed 3.75 times higher risk of NAFLD than the low-risk group (non-smokers with C/G genotype) in a multiple logistic analysis after adjusting for the confounders (p < 0.001), but no departure from additivity was found. Our results indicated that the C/C genotype and smoking were significant independent risk factors for NAFLD. The possible synergistic effects of genotype and smoking may promote the development of NAFLD by aggravating oxidative stress, which supports the hypothesis that oxidative stress contributes to the development of NAFLD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Publishing year

2012

Language

English

Pages

255-259

Publication/Series

Molecular and Cellular Endocrinology

Volume

348

Issue

1

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • Pro/Ala variant
  • PPARG gene
  • Smoking
  • Synergistic effect
  • Non-alcoholic
  • fatty liver

Status

Published

Research group

  • Diabetes - Epigenetics

ISBN/ISSN/Other

  • ISSN: 1872-8057