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Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

Genes & Immunity volume 6, pages 347–357 (2005)Cite this article

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.

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Acknowledgements

We thank Sadeep Shrestha, Yvette Berthier-Schaad, Shanise Hill, Melissa Levasseur, James Lautenberger, Audrey Majeske, Andrea Moser, Kevin Scott, and Kai Zhao from the Laboratory of Genomic Diversity of the National Cancer Institute for helpful discussions and generous help with the laboratory design and analysis. Allen Kane and Carolyn Whistler of the Scientific Publications Graphics and Media at SAIC-Frederick were helpful in preparing this manuscript for publication. The experiments performed and described in this paper were carried out with informed consent and Institutional Review Board approval at the respective institutions. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This publication has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health (NIH) under Contract No. NO1-CO-12400, and by NIH Grants DA13324 and DA00441.

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Authors and Affiliations

  1. Laboratory of Genomic Diversity, National Cancer Institute at Frederick, Frederick, MD, USA

    T K Oleksyk, A L Truelove, S J O'Brien & M W Smith

  2. Basic Research Program, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, MD, USA

    T K Oleksyk, A L Truelove & M W Smith

  3. Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    C L Thio, G D Kirk & D L Thomas

  4. Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    J J Goedert

  5. Rho Inc., Chapel Hill, NC, USA

    S M Donfield

  6. Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA

    G D Kirk & D L Thomas

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Oleksyk, T., Thio, C., Truelove, A. et al. Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance. Genes Immun 6, 347–357 (2005). https://doi.org/10.1038/sj.gene.6364188

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