Methylenetetrahydrofolate reductase C677T mutation and nonalcoholic fatty liver disease

Dig Dis Sci. 2007 May;52(5):1183-6. doi: 10.1007/s10620-006-9565-7. Epub 2007 Mar 14.


A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is known as one of the causes of hyperhomocyteinemia. The oxidation products of homocysteine can initiate lipid peroxidation, which has a central role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to assess the possible role of the MTHFR C677T mutation in the progression of simple steatosis to an advanced form of NAFLD. Thirty-four patients with NAFLD diagnosed by histologic analysis and 282 healthy controls were included in the study. The discrimination of nonalcoholic steatohepatitis (NASH) from another NAFLD was made by NAFLD activity score (NAS), and a NAS>or=5 was considered NASH. Patients with either NASH or nonalcoholic fatty liver (NAFL) and controls were evaluated for frequency of the MTHFR C677T mutation. The frequency of the MTHFR C677T mutation was 53.5% (CT, 44.7%; TT, 8.9%) in controls and 41.5% (CT, 37.7%; TT, 3.8%) in patients (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.34-1.12). There was no statistical difference in the frequency of this genotype between patients with NAFL and those with NASH (36% [CT, 28%; TT, 8%] vs 46.4% [CT, 46.4; TT, 0%]; OR, 0.65; 95% CI, 0.22-1.96). According to this study, the MTHFR C677T mutation does not seem to be a risk factor for the progression of NAFL to NASH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cytosine
  • Disease Progression
  • Fatty Liver / genetics*
  • Fatty Liver / pathology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Mutation*
  • Odds Ratio
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Thymine
  • Turkey


  • Cytosine
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Thymine