ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C

Nature. 2010 Mar 18;464(7287):405-8. doi: 10.1038/nature08825. Epub 2010 Feb 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Anemia, Hemolytic / chemically induced*
  • Anemia, Hemolytic / complications
  • Anemia, Hemolytic / genetics*
  • Antiviral Agents
  • Chromosomes, Human, Pair 20
  • Continental Population Groups / genetics
  • Europe / ethnology
  • Genetic Variation / genetics*
  • Genome-Wide Association Study
  • Hemoglobins / deficiency
  • Hemoglobins / metabolism
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Pyrophosphatases / deficiency
  • Pyrophosphatases / genetics*
  • Pyrophosphatases / metabolism
  • Ribavirin / therapeutic use
  • United States

Substances

  • Antiviral Agents
  • Hemoglobins
  • Ribavirin
  • Pyrophosphatases
  • inosine triphosphatase
  • ITPA protein, human