Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection
- 26 August 2003
- journal article
- research article
- Published by Springer Science and Business Media LLC in Immunogenetics
- Vol. 55 (6), 362-369
- https://doi.org/10.1007/s00251-003-0594-5
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.Keywords
This publication has 40 references indexed in Scilit:
- IL-10 and TNF-α polymorphisms and the recovery from HCV infectionHuman Immunology, 2003
- Differential regulation of interleukin-10 production by genetic and environmental factors – a twin studyGenes & Immunity, 2002
- Polymorphisms in the interleukin-10, tumor necrosis factor-α, and transforming growth factor-β1 genes in chronic hepatitis C patients treated with interferon and ribavirinJournal of Hepatology, 2002
- Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infectionHepatology, 2001
- Epidemiology of hepatitis C virus infection in seven European Union countries: a critical analysis of the literatureEuropean Journal of Gastroenterology & Hepatology, 2000
- AN INVESTIGATION OF POLYMORPHISM IN THE INTERLEUKIN‐10 GENE PROMOTEREuropean Journal of Immunogenetics, 1997
- Histological grading and staging of chronic hepatitisJournal of Hepatology, 1995
- Monte Carlo tests for associations between disease and alleles at highly polymorphic lociAnnals of Human Genetics, 1995
- Interleukin-10Annual Review of Immunology, 1993
- Treatment of Chronic Non-A, Non-B Hepatitis with Recombinant Human Alpha InterferonNew England Journal of Medicine, 1986