title: ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C.
abstract: Chronic infection with the hepatitis C virus (HCV) affects 170 million people worldwide and is an important cause of liver-related morbidity and mortality. The standard of care therapy combines pegylated interferon (pegIFN) alpha and ribavirin (RBV), and is associated with a range of treatment-limiting adverse effects. One of the most important of these is RBV-induced haemolytic anaemia, which affects most patients and is severe enough to require dose modification in up to 15% of patients. Here we show that genetic variants leading to inosine triphosphatase deficiency, a condition not thought to be clinically important, protect against haemolytic anaemia in hepatitis-C-infected patients receiving RBV.
authors.affiliation: Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ge
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Gumbs
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Urban
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Latasha D
authors.initials: LD
authors.lastname: Little
authors.forename: Ping
authors.initials: P
authors.lastname: Qiu
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Bertelsen
authors.forename: Mark
authors.initials: M
authors.lastname: Watson
authors.forename: Amelia
authors.initials: A
authors.lastname: Warner
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.forename: Clifford
authors.initials: C
authors.lastname: Brass
authors.forename: Janice
authors.initials: J
authors.lastname: Albrecht
authors.forename: Mark
authors.initials: M
authors.lastname: Sulkowski
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
mesh_terms: D000483:Alleles; D000743:Anemia, Hemolytic / Q000139:chemically induced* / Q000150:complications / Q000235:genetics*; D000998:Antiviral Agents; D002890:Chromosomes, Human, Pair 20; D005060:Europe / Q000208:ethnology; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006454:Hemoglobins / Q000172:deficiency / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011755:Pyrophosphatases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D044469:Racial Groups / Q000235:genetics; D012254:Ribavirin / Q000627:therapeutic use; D014481:United States; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D011755:Pyrophosphatases; D012254:Ribavirin; D000097630:Inosine Triphosphatase; C511829:ITPA protein, human