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An analysis of tumor necrosis factor α gene polymorphisms and haplotypes with natural clearance of hepatitis C virus infection

Genes & Immunity volume 5, pages 294–300 (2004)Cite this article

Abstract

The cytokine tumor necrosis factor alpha (TNF-α) is important in generating an immune response against a hepatitis C virus (HCV) infection. The functions of TNF-α may be altered by single-nucleotide polymorphisms (SNPs) in its gene, TNF. We hypothesized that SNPs in TNF may be important in determining the outcome of an HCV infection. To test this hypothesis, we typed nine TNF SNPs in a cohort of individuals with well-defined HCV outcomes. Three of these SNPs were typed in a second cohort. Data were analyzed using logistic regression stratifying by ethnicity, since rates of HCV clearance differ in black subjects versus white subjects. The SNP −863A was associated with viral clearance in black subjects (odds ratios (OR) 0.52, 95% confidence interval (CI) 0.29–0.93). Furthermore, the common wild-type haplotype −863C/−308G was associated with viral persistence in black subjects (OR 1.91, 95% CI 1.24–2.95). These findings were independent of linkage with human leukocyte antigen (HLA) alleles. Further study of this polymorphism and haplotype is needed to understand these associations and the role of TNF-α in determining outcomes of HCV infection.

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Acknowledgements

This work was supported by NIH Grants DA00441, DA12568, DA04334, DA13324, and DK56415. MHCS is supported by National Cancer Institute Contract N01-CP-33002 with Research Triangle Institute. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract no NO1-CO-12400. The publisher or recipient acknowledges rights of the US Government to retain a nonexclusive, royalty-free license in, and to any copyright covering the article. We thank the study subjects for participating in this study.

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Authors and Affiliations

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

    C L Thio, T Mosbruger, J Astemborski & D L Thomas

  2. Viral Epidemiology Branch, National Cancer Institute, Rockville, MD, USA

    J J Goedert

  3. New York Academy of Medicine, New York, NY, USA

    D Vlahov

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

    S A Strathdee

  5. Laboratory of Genomic Diversity, Frederick, MD, USA

    S J O'Brien

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  1. C L Thio
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Correspondence to C L Thio.

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Thio, C., Goedert, J., Mosbruger, T. et al. An analysis of tumor necrosis factor α gene polymorphisms and haplotypes with natural clearance of hepatitis C virus infection. Genes Immun 5, 294–300 (2004). https://doi.org/10.1038/sj.gene.6364072

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