Viral genotype-specific role of PNPLA3, PPARG, MTTP, and IL28B in hepatitis C virus-associated steatosis

J Hepatol. 2011 Sep;55(3):529-535. doi: 10.1016/j.jhep.2010.12.020. Epub 2011 Jan 12.


Background & aims: Steatosis is a prominent feature of hepatitis C, especially in patients infected with genotype 3. The analysis of genetic polymorphisms influencing steatosis in chronic hepatitis C has been limited by the studies' small sample size, and important single nucleotide polymorphisms (SNPs), such as those in the patatin-like phospholipase family 3 protein (PNPLA3), were never evaluated.

Methods: We analyzed the role of SNPs, from 19 systematically selected candidate genes, on steatosis in 626 Caucasian hepatitis C virus (HCV) infected patients. SNPs were extracted from a genome-wide association-generated dataset. Associations of alleles with the presence and/or different severity of steatosis were evaluated by univariate and multivariate logistic regression, accounting for all relevant covariates.

Results: The risk of steatosis was increased by carriage of I148M in PNPLA3, but only in patients with HCV genotypes non-3 (odds ratio [OR]=1.9, 95% confidence interval [CI]=1.6-2.3, p<0.001) and similar, albeit weaker associations were found for SNPs in peroxisome proliferator-activated receptor-γ (PPARG) and interleukin-28B (IL28B). Carriage of a SNP in the microsomal triglyceride transfer protein (MTTP) increased the risk of steatosis, but only in patients with HCV genotype 3 (rs1800803, OR=3.4, 95% CI=2.4-4.9, p=0.001).

Conclusions: The rs738409 SNP in PNPLA3 is associated with an increased risk of steatosis in patients infected with HCV genotypes non-3. Host genes affect steatosis depending on the infecting HCV genotype, suggesting their interaction with viral factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / genetics
  • Fatty Liver / complications
  • Fatty Liver / genetics*
  • Fatty Liver / virology
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Interferons
  • Interleukins / genetics
  • Lipase / genetics
  • Logistic Models
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • PPAR gamma / genetics
  • Polymorphism, Single Nucleotide*
  • Severity of Illness Index


  • Carrier Proteins
  • interferon-lambda, human
  • Interleukins
  • Membrane Proteins
  • PPAR gamma
  • microsomal triglyceride transfer protein
  • Interferons
  • Lipase
  • adiponutrin, human