1. Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA
2. Duke Clinical Research Institute and Division of Gastroenterology, School of Medicine, Duke University, Durham, North Carolina 27705, USA
3. Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA
4. Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Correspondence to: David B. Goldstein¹ Correspondence and requests for materials should be addressed to D.B.G. (Email: d.goldstein@duke.edu).

Abstract

Chronic infection with hepatitis C virus (HCV) affects 170 million people worldwide and is the leading cause of cirrhosis in North America¹. Although the recommended treatment for chronic infection involves a 48-week course of peginterferon--2b (PegIFN--2b) or --2a (PegIFN--2a) combined with ribavirin (RBV), it is well known that many patients will not be cured by treatment, and that patients of European ancestry have a significantly higher probability of being cured than patients of African ancestry. In addition to limited efficacy, treatment is often poorly tolerated because of side effects that prevent some patients from completing therapy. For these reasons, identification of the determinants of response to treatment is a high priority. Here we report that a genetic polymorphism near the IL28B gene, encoding interferon--3 (IFN--3), is associated with an approximately twofold change in response to treatment, both among patients of European ancestry (P = 1.06  10^-25) and African-Americans (P = 2.06  10^-3). Because the genotype leading to better response is in substantially greater frequency in European than African populations, this genetic polymorphism also explains approximately half of the difference in response rates between African-Americans and patients of European ancestry.

1. Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA
2. Duke Clinical Research Institute and Division of Gastroenterology, School of Medicine, Duke University, Durham, North Carolina 27705, USA
3. Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA
4. Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Correspondence to: David B. Goldstein¹ Correspondence and requests for materials should be addressed to D.B.G. (Email: d.goldstein@duke.edu).