Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection
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The natural outcome and response to treatment in hepatitis C virus (HCV) infection varies between individuals. Whereas some variation may be attributable to viral and environmental variables, it is probable that host genetic background also plays a significant role. Interleukin (IL)-10 has a key function in the regulation of cellular immune responses and in the suppression of pro-inflammatory cytokine secretion. Functional polymorphisms in the IL-10 gene have been described. We investigated the role of these polymorphisms in the outcome of HCV infection, treatment response and development of fibrosis in a case-control association study. Self-limiting infection was associated with the IL-10 (−592) AA genotype (OR=2.05; P=0.028). Persistent infection was associated with the IL-10 (−1082) GG genotype (OR=0.48; P=0.018). Sustained response to interferon therapy was associated with the IL-10 (−1082) GG genotype (OR=2.28; P=0.005) and the haplotype GCC (OR=2.27; P=0.020). The IL-10 (−1082) AA genotype and the ATA/ATA and ACC/ACC homozygous haplotypes were more frequent among patients with rapid fibrosis. Furthermore, the microsatellites IL-10.R and IL-10.G were associated with interferon response with IL-10R.2 conveying susceptibility (OR=1.80; P=0.034), and IL-10R.3 and IL-10.G13 being protective (OR=0.47; P=0.003 and OR=0.59; P=0.042, respectively). We conclude that polymorphisms in the IL-10 promoter appear to have some influence on the outcome of HCV infection, treatment and development of fibrosis.
KeywordsSelf-limiting infection Interferon Fibrosis Genotype Disease association Hepatitis C
HENCORE is the Hepatitis C European Network for Cooperative Research. The participants were: Howards C Thomas, Mark R Thursz (Faculty of Medicine, Imperial College School of Medicine at St Mary's Hospital, Praed Street, London W2 1NY, UK), Pierre Pradat PhD, Christian Trepo (Hopitaux de Lyon, 1 Place de l'Hopital, 69288 Lyon Cedex 02, France), Juan Esteban MD (Hospital General Valle Hebron, Pasea Valle, Hebron S/U o8035, Barcelona, Spain), Stephanos Hadziyannis MD (University of Athens Medical School, 2nd Department of Medicine, Hippokration Hospital, 114 Vasilissis Sophias Avenue, Athens 610, Greece), Michael Manns PhD, Hans Tillmann MD (Medizinische Hochschule Hannover, Carl Neuburg Strasse 1, 30623 Hannover, Germany), Alfredo Alberti MD, Liliana Chemello MD (Department of Clinical and Experimental Medicine, Via Guistiniani 2, 35126 Padua, Italy), Giorgio Saracco MD, Mario Rizzetto PhD (Department of Gastroenterology, Molinette Hospital, Turin, Italy), Jean-Henrik Braconier MD (Department of Infectious Diseases, University Hospital, Lund, Sweden). This work was generously supported by Roche Discovery, Welwyn, UK and the Charmot-Horton Foundation. M.W. is a Medical Research Council of Great Britain clinical training fellow. A.V.S.H. is a Wellcome Trust Principal Fellow.
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