Microsomal triglyceride transfer protein polymorphism (-493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C

Liver Int. 2009 Apr;29(4):557-65. doi: 10.1111/j.1478-3231.2008.01892.x. Epub 2008 Oct 10.

Abstract

Background: Hepatic steatosis may promote progression of chronic hepatitis C (CHC). Microsomal triglyceride transfer protein (MTP) is required for assembly and secretion of ApoB lipoprotein and is implicated in hepatitis C virus (HCV)-related steatosis. The MTP -493G/T polymorphism may promote liver fat accumulation, but its role in HCV-related steatosis is still unclear.

Methods: Two hundred ninety-eight CHC patients were studied and genotyped for MTP -493G/T variants. Hepatic MTP mRNA expression and activity were determined in a subgroup.

Results: Patients with grades 2/3 steatosis were older, had a higher body mass index (BMI), more advanced fibrosis and lower MTP mRNA expression and carried more often HCV genotype 3 and the MTP T allele. Age, BMI, HCV-3 and MTP T allele [odds ratio (OR) 2.05; 95% confidence interval (CI) 1.2-3.53; P=0.009] were independent risk factors for steatosis grades 2/3, and in HCV genotype non-3 patients, the MTP T allele was the strongest predictor for steatosis grade 2/3 (OR 2.17; 95% CI 1.22-3.86; P=0.008). Moreover, TT carriers had higher high-density lipoprotein (65.6+/-14.6 vs 56.1+/-16.2 mg/dl; P=0.003) and apolipoprotein AI (1.80+/-0.3 vs 1.60+/-0.3 g/L; P=0.005) levels than G allele carriers.

Conclusions: Chronic hepatitis C patients with the MTP -493T allele reveal higher grades of steatosis, indicating a relevant contribution to liver fat accumulation, particularly in HCV non-3 patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoprotein A-I / blood
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Disease Progression
  • Fatty Liver / genetics*
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / pathology
  • Humans
  • Lipoproteins, HDL / blood
  • Male
  • Microsomes, Liver / metabolism
  • Middle Aged
  • Polymorphism, Genetic*
  • RNA, Messenger / metabolism
  • Risk Factors

Substances

  • Apolipoprotein A-I
  • Carrier Proteins
  • Lipoproteins, HDL
  • RNA, Messenger
  • microsomal triglyceride transfer protein