Z Gastroenterol 2006; 44 - P233
DOI: 10.1055/s-2006-950830

Pro12Ala mutation of peroxisome proliferator-activated receptor γ in patients with non-alcoholic fatty liver disease

J Rey 1, HU Kasper 2, M Scheffler 1, I Wedemeyer 1, N Bektaz 3, G Gerken 4, HP Dienes 1, A Canbay 4, M Odenthal 1
  • 1University Clinic Cologne, Institute of Pathology, Cologne, Germany
  • 2Clemens Hospital Münster, Institute of Pathology, Münster, Germany
  • 3Helios Clinic Wuppertal, Institute of Pathology, Wuppertal, Germany
  • 4University Clinic Essen, Clinic of Gastroenterology and Hepatology, Essen, Germany

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver diseases ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis (NASH), to cirrhosis as the irreversible, fibrotic form with advanced scarring of the liver. Peroxisome proliferator-activated receptor γ(PPAR γ) is a member of ligand-activated transcription factors and plays an important role in many cellular functions including lipid metabolism, cell proliferation, adipogenesis and inflammatory and fibrogenic signaling. In the present study, we tested the occurrence of the Ala12Pro mutation of the PPAR γ 2 gene associated with impaired PPAR γ activity.

Methods: 240 liver biopsies from patients including 135 with no (NAFLD) and 105 with regular alcohol abusus (AFLD, alcoholic fatty liver disease) were monitored and categorized according to the Nonalcoholic Steatohepatitis Clinical Research Network (Kleiner et al., Hepatology 2005). DNA from these 240 formalin fixed and paraffin embedded liver biopsies were extracted and taken for Real Time PCR using LNA probes to discriminate alleles. In addition, DNA from 200 samples of healthy blood donors were extracted and used as a control collective.

Results: In the control collective 22% of cases showed heterozygous and 2% homozygous occurrence of the Ala12 PPAR γ 2 allele. In the collective of patients with NAFLD and AFLD the overall distribution of homo- and heterozygous Ala12 mutation corresponds to the pattern found in the control collective of blood donors. However, in the group of NAFLD patients shown to have progressive fibrosis of grade 2 to 4, the Ala12 mutation appears more often than in patients with no or moderate fibrosis or the control group. In order to achieve statistical significance the number of NAFLD specimen will be expanded and other polymorphisms of genes, affecting fat metabolism and fibrosis, will be also considered.

Conclusion: Analyses of the Pro12Ala mutation of the PPAR γ2 gene indicates that the Ala12 substitution might be involved in fibrosis progression and should be tested as a putative prognostic marker of NAFLD.