Effect of peroxisome proliferator-activated receptors-gamma and co-activator-1alpha genetic polymorphisms on plasma adiponectin levels and susceptibility of non-alcoholic fatty liver disease in Chinese people

Liver Int. 2008 Mar;28(3):385-92. doi: 10.1111/j.1478-3231.2007.01623.x. Epub 2007 Nov 12.

Abstract

Background/aims: Peroxisome proliferator-activated receptors-gamma (PPAR-gamma) and its co-activator-1alpha (PGC-1alpha) are involved in the regulation of lipid and glucose metabolisms. This study aimed to investigate the genetic polymorphisms of PPAR-gamma and PGC-1alpha in Chinese people and their influence on plasma adiponectin levels and non-alcoholic fatty liver disease (NAFLD) susceptibility.

Methods: Ninety-six patients with NAFLD and 96 healthy controls were included. The single nucleotide polymorphisms (SNPs) of C161T PPAR-gammaand Gly482Ser PGC-1alpha genes were analysed by polymerase chain reaction and restriction fragment length polymorphism.

Result: The CC, CT and TT genotypic distributions of the NAFLD group were significantly different from those of controls (55.2, 39.6, 5.2 vs. 74.0, 25.0, 1.0%; P=0.015). The allelic frequencies of C and T were also different between the two groups (P=0.004). As for the PGC-1alpha gene, there was no difference of the genotypic and allelic frequencies between the two groups (P>0.05). In NAFLD patients, the plasma adiponectin concentrations were lower in the PPAR-gamma CT/TT genotypes compared with those in the CC genotype group (3.0+/-0.6 vs. 4.3+/-0.9, P=0.02). Multivariate logistic regression analysis showed that CT/TT genotypes of PPAR-gamma, TG, waist hip ratio, hypoadiponectinaemia and homoeostasis model assessment (HOMA)-IR were the risk factors for NAFLD.

Conclusion: SNPs in the PPAR-gamma, but not PGC-1alpha, gene are associated with NAFLD susceptibility possibly through the adiponectin pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood*
  • Asian People
  • Body Weights and Measures
  • Fatty Liver / genetics*
  • Fatty Liver / metabolism
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Logistic Models
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Adiponectin
  • Heat-Shock Proteins
  • PPAR gamma
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors