The impact of human gene polymorphisms on HCV infection and disease outcome

Semin Liver Dis. 2011 Nov;31(4):375-86. doi: 10.1055/s-0031-1297926. Epub 2011 Dec 21.

Abstract

In recent years, some genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with hepatitis C viral containment, treatment response, and disease progression. IL28B is a gene on chromosome 19, coding for interferon-λ3, and two polymorphisms upstream of this the gene have been strongly associated with clinical outcomes after treatment for the hepatitis C virus (HCV). The IL28B polymorphisms have additionally been associated with spontaneous clearance. The mechanism has yet to be clearly defined, but appears to involve differential responsiveness to interferon signaling between the favorable and unfavorable genotypes. ITPA is a gene on chromosome 20, coding for inosine triphosphatase, and polymorphisms on this gene have been associated with ribavirin-induced hemolytic anemia. Functional variants of ITPA have been identified that have decreased enzymatic activity, which appear to protect against anemia. Finally, PNPLA3 polymorphisms were initially described as predictors of nonalcoholic fatty liver disease, but have recently been associated with disease progression in HCV.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / pharmacology
  • Disease Progression
  • Genetic Predisposition to Disease
  • Genotype
  • Hepacivirus / pathogenicity*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / physiopathology
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Interleukins / immunology
  • Lipase / genetics*
  • Lipase / immunology
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology
  • Polymorphism, Single Nucleotide / physiology
  • Protease Inhibitors / pharmacology
  • Pyrophosphatases / genetics*
  • Pyrophosphatases / immunology

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interleukins
  • Membrane Proteins
  • Protease Inhibitors
  • Interferons
  • Lipase
  • adiponutrin, human
  • Pyrophosphatases
  • ITPA protein, human