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Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR

Genes & Immunity volume 4, pages 411–419 (2003)Cite this article

Abstract

Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PKR). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position −88 in the MxA gene promoter in self-limiting HCV infection (OR=0.56; 95% CI: 0.35–0.8; P=0.010) and in nonresponders to therapy (OR=0.49; 95% CI: 0.25–0.95; P=0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR=0.22 95% CI: 0.07–0.67; P=0.002). A polymorphism in the 3′-untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR=0.43; 95% CI: 0.21–0.86; P=0.010). A polymorphism at position −168 in the promoter region of the PKR gene was associated with self-limiting infection (CT genotype: OR=2.75; 95% CI: 1.45–5.24; P=0.002). Further associations were found with a CGG trinucleotide repeat in the 5′UTR region of the PKR gene. Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome.

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Acknowledgements

The HENCORE group (Hepatitis C European Network for Cooperative Research) includes: Robert Goldin and Rhiannon Yallop (London, UK), Pierre 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), Jean-Henrik Braconier (Stockholm, Sweden).

Special thanks go to the patients and their families for their cooperation and participation in this study. This work was funded by Roche Discovery, Welwyn, UK. We are grateful for financial support from the UK Department of Health; the views expressed in this publication are those of the authors and not necessarily those of the Department of Health. AJF was supported by a Wellcome Trust Research Training and AVSH by a Wellcome Trust Principal Research Fellowship. MW is an MRC Clinical Training Fellow. We are also indebted to Dr Carla Venturi-Passini and Dr Salvatori Lobello for their technical assistance.

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Authors and Affiliations

  1. Hepatology Section, Imperial College, Faculty of Medicine, Imperial College of Science, Medicine and Technology at St Mary's Hospital, London, UK

    S Knapp, L J Yee, M Wright, H C Thomas & M R Thursz

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

    L J Yee

  3. Head of Virological Diseases, Welwyn Garden City, UK

    M Graves

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

    A J Frodsham, B J W Hennig, S Hellier, L Zhang & A V S Hill

  5. Department of Gastroenterology, University of Padua, Padua, Italy

    M Chiaramonte

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  1. S Knapp
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Correspondence to M R Thursz.

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Knapp, S., Yee, L., Frodsham, A. et al. Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR. Genes Immun 4, 411–419 (2003). https://doi.org/10.1038/sj.gene.6363984

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