title: The impact of human gene polymorphisms on HCV infection and disease outcome.
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.
authors.affiliation: GI Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. eschaefer@partners.org
authors.forename: Esperance A K
authors.initials: EA
authors.lastname: Schaefer
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016174:Hepacivirus / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D008049:Lipase / Q000235:genetics* / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology; D011755:Pyrophosphatases / Q000235:genetics* / Q000276:immunology; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; D011480:Protease Inhibitors; D011755:Pyrophosphatases; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase