Genetic variation in the peroxisome proliferator activated receptor-gamma gene is associated with histologically advanced NAFLD

Dig Dis Sci. 2012 Apr;57(4):952-7. doi: 10.1007/s10620-011-1994-2. Epub 2011 Dec 9.


Background: The peroxisome proliferator activated receptor-gamma (PPARG) is a nuclear receptor that regulates adipocyte differentiation, insulin sensitivity and lipid metabolism, thus, it represents a good candidate gene for non-alcoholic fatty liver disease (NAFLD).

Purpose and method: We investigated the association of two PPARG variants (Pro12Ala and C1431T) with NAFLD and its histological features. DNA was extracted from 274 archived, formalin-fixed liver biopsy specimens from 212 patients with NAFLD and 62 controls with normal liver histology.

Results: Individual SNPs did not show significant association with NAFLD or its histological features. A haplotype comprised of both minor alleles (GT) was less enriched whereas a haplotype comprised of the two major alleles (CC) was more enriched in subjects with NAFLD compared to controls [9.3% vs. 28.1% for GT (P = 0.001, OR 0.26 (range 0.14-0.48) and 80.4% vs. 64.8% for CC (P = 0.037, OR 2.23 (range 1.30-3.81)]. Both haplotypes were significantly associated with steatosis and fibrosis. The GT haplotype was also associated with lobular inflammation.

Conclusions: Genetic variation in PPARG is associated with NAFLD, and the GT haplotype is associated with inflammatory and fibrotic changes that denote histologically advanced NAFLD.

MeSH terms

  • Adult
  • Fatty Liver / genetics*
  • Fatty Liver / pathology
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Liver / pathology
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • PPAR gamma / genetics*
  • Polymorphism, Single Nucleotide*


  • PPAR gamma