1. ¹Laboratory of Genomic Diversity, National Cancer Institute at Frederick, Frederick, MD, USA
2. ²Basic Research Program, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, MD, USA
3. ³Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
4. ⁴Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
5. ⁵Rho Inc., Chapel Hill, NC, USA
6. ⁶Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA

Correspondence: Dr MW Smith, Basic Research Program, SAIC Frederick & Laboratory of Genomic Diversity, National Cancer Institutes, Bldg 560, Frederick, MD 21702, USA. E-mail: smithm@ncifcrf.gov

Received 15 November 2004; Revised 31 January 2005; Accepted 2 February 2005; Published online 7 April 2005.

Abstract

Hepatitis C virus (HCV) is an infectious blood-borne pathogen that usually persists as a chronic infection. However, approximately 15% of the time, patients can clear the virus, indicating that host differences could be critical in determining the course of HCV infection. The inflammatory response is crucial to resolving or failing to resolve an acute HCV infection. Some previous reports have implicated interleukin 10 (IL10) polymorphisms with successful anti-HCV therapy and natural viral clearance. We tested 54 single nucleotide polymorphisms (SNPs) in the IL10 region (300 kb and 24 within the IL10 gene itself), which contains 13 genes including the IL10 immunomodulatory paralogs IL19, IL20, and IL24, for association with HCV clearance vs persistence. SNPs from two haplotype block regions, one at IL10 and the other from IL19/IL20, were associated with HCV clearance in African Americans (91 clearance cases and 183 chronically infected matched controls; P=0.05–0.002) while with expectation-maximization algorithm-reconstructed haplotypes, these associations remained (P=0.05–0.002). However, no significant associations were detected in European Americans (108 clearance and 245 chronic). Our results indicate that variants of the immunomodulatory IL10 and IL19/IL20 genes may be involved in natural clearance of HCV in the African-American population.