Genetic variation in IL28B and spontaneous clearance of hepatitis C virus
By David L. Thomas, C. Thio, Maureen P. Martin, Y. Qi, D. Ge, C. O’hUigin, J. Kidd, K. Kidd, S. Khakoo, G. Alexander and 9 more. Nature, 2009
2,249 citations recorded by the source corpus.
Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide. Most (70–80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. Epidemiological, viral and host factors have been associated with the differences in HCV clearance or persistence, and studies have demonstrated that a strong host immune response against HCV favours viral clearance. Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-λ3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment. To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus (n = 388) or had persistent infection (n = 620). We show that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry. To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.
Subfields: Epidemiology, Hepatology
View Paper: https://www.semanticscholar.org/paper/bbb27f607de29dcfcf01e130c4dcbace55376267
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Citations in the corpus
- Into the Eye of the Cytokine Storm (2012, background): “Several GWAS have also identified variants of IFN- 3 that were associated with spontaneous resolution and successful treatment of hepatitis C virus (HCV) infection (55, 140).”
- An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases (2011, background): “polymorphisms associated with spontaneous and treatment-induced clearance of HCV infection.(18,19) Although PegIFN and RBV remain vital components of therapy, the emergence of DAAs has led to a substantial improvement in SVR rates and the option of abbreviated therapy in many patients with genotype ”
- Next generation disparities in human genomics: concerns and remedies. (2009, background): “Thomas et al. argued that the IL28B variant shows differential geographic allele frequencies because of geographic differences in the burden of one or more viruses that IL28B helps to control [ 18 ].”
- EASL Clinical Practice Guidelines: management of hepatitis C virus infection. (2011, background): “The distribution of IL28B polymorphisms varies between different populations worldwide and helps to explain heterogeneity in response to interferonbased treatments in different ethnic or racial groups [30].”