ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C
Open accessAbstract
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.
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In chronic hepatitis C, the initial GWAS signal for protection against anemia captures two less common causal coding variants at ITPA.
“The case of protection against anemia in chronic hepatitis C, where the initial GWAS discovery clearly captures two less common causal coding variants at the ITPA locus, is a good example110.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [110]
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- Authors
- Fellay, J., Thompson, A. J., Ge, D., Gumbs, C. E., Urban, T. J., Shianna, K. V., Little, L. D., Qiu, P., Bertelsen, A. H., Watson, M., Warner, A., Muir, A. J., Brass, C., Albrecht, J., Sulkowski, M., McHutchison, J. G., & Goldstein, D. B.
- Affiliations
- Duke University (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Johns Hopkins University (US)
- Corresponding author
- McHutchison, John G.
- Goldstein, David B.
- ORCID
- Venue
- Nature
- Published
- 2010-02-21
- Volume
- 464
- Issue
- 7287
- Pages
- 405-408
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2109235725
- Cited by
- 441
- References
- 28
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 10 · 2018: 13 · 2017: 24 · 2016: 47 · 2015: 41 · 2014: 42 · 2013: 58 · 2012: 69
- FWCI
- 49.23
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- chronic hepatitis C, pegylated interferon, ribavirin, drug-induced anemia, pharmacogenetics
- MeSH terms
- Inosine Triphosphatase, Alleles, Anemia, Hemolytic, Antiviral Agents, Chromosomes, Human, Pair 20, Europe, Hemoglobins, Humans, Pyrophosphatases, Ribavirin, United States, Genetic Variation, Hepatitis C, Chronic, Polymorphism, Single Nucleotide, Racial Groups, Genome-Wide Association Study
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