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Inducible nitric oxide synthase gene (NOS2A) haplotypes and the outcome of hepatitis C virus infection

Genes & Immunity volume 5, pages 183–187 (2004)Cite this article

Abstract

Inducible nitric oxide synthase (iNOS) is an important molecule involved in the host defense against infectious agents. iNOS is encoded by the NOS2A gene and well-defined haplotypes exist with respect to this gene. We examined whether these haplotypes were associated with the outcome of hepatitis C virus (HCV) infection in 619 Caucasian patients from seven European liver centres. We observed five major haplotypes: (−277A)+(−1026G)+(−1659C): haplotype 1; (−277G)+(−1026T)+(−1659C): haplotype 2; (−277G)+(−1026G)+(−1659C): haplotype 3; (−277G)+(−1026T)+(−1659T): haplotype 4; and (−277A)+(−1026T)+(−1659C): haplotype 5. Distributions of these haplotypes are comparable with those of previous studies. Homozygotes for haplotype 2 or those with haplotypes 2/4 were more likely than those with the 1/1 (wild type) combination to have self-limiting infections (odds ratios (OR)=3.43; 95% confidence intervals (95% CI): 1.10–8.0; P=0.0206 and OR=5.15; 95% CI: 1.32–14.32; P=0.0018, respectively). Conversely, carriage of haplotype 1 was associated with the lack of self-limiting disease (OR=0.48; 95% CI: 0.27–0.83; P=0.009). The effect was mainly among males (OR=0.41; 95% CI: 0.182–0.942; P=0.031 for males, and OR=0.55; 95% CI: 0.24–1.37; P=0.136 for women). Carriage of haplotype 1 was not associated with initial response (P=0.268) or sustained response (P>0.171). Combinations of haplotypes 1/4 were more likely to respond to interferon monotherapy in comparison of initial responders to nonresponders (OR=2.25; 95% CI: 1.05–5.68; P=0.0275).

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Acknowledgements

The HENCORE group (Hepatitis C European Network for Cooperative Research) includes: Robert Goldin and Rhiannon Yallop (London, UK), Pierrre Pradat and Christian Trepo (Lyon, France), Juan Esteban (Barcelona, Spain), Stephanos Hadziyannis (Athens, Greece), Michael Manns and Hans Tillmann (Hannover, Germany), Alfredo Alberti and Liliana Chemello (Padova, Italy), Giorgio Saracco (Torino, Italy), Mario Rizzetto (Turin, Italy), and Jean-Henrik Braconier (Stockholm, Sweden). This work was supported by Roche Discovery, Welwyn, UK. Mark Wright was supported by the Medical Research Council. Angela Frodsham was supported by a Wellcome Trust Fellowship. Adrian VS Hill is a principal Wellcome Trust Fellow.

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Author notes

  1. LJ Yee: From 1 April 2004: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 152621, USA. E-mail: yeel@edc.pitt.edu

Authors and Affiliations

  1. Hepatology Division, Imperial College Faculty of Medicine at St Mary's Hospital, London, UK

    LJ Yee, S Knapp, M Wright, HC Thomas & MR Thursz

  2. Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, UK

    LJ Yee

  3. School of Paediatrics and Child Health, University of Western Australia, Perth, Australia

    D Burgner

  4. Wellcome Trust Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK

    BJW Hennig, AJ Frodsham & AVS Hill

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  1. LJ Yee
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Yee, L., Knapp, S., Burgner, D. et al. Inducible nitric oxide synthase gene (NOS2A) haplotypes and the outcome of hepatitis C virus infection. Genes Immun 5, 183–187 (2004). https://doi.org/10.1038/sj.gene.6364054

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