Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection.


Knapp, S; Hennig, BJ; Frodsham, AJ; Zhang, L; Hellier, S; Wright, M; Goldin, R; Hill, AV; Thomas, HC; Thursz, MR; (2003) Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection. Immunogenetics, 55 (6). pp. 362-9. ISSN 0093-7711 DOI: https://doi.org/10.1007/s00251-003-0594-5

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Abstract

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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) > Dept of Nutrition and Public Health Interventions Research (2003-2012)
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 12942209
Web of Science ID: 185394600002
URI: http://researchonline.lshtm.ac.uk/id/eprint/13395

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