Immunogenetics

, Volume 55, Issue 6, pp 362–369

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

  • Susanne Knapp
  • Branwen J. W. Hennig
  • Angela J. Frodsham
  • Lyna Zhang
  • Simon Hellier
  • Mark Wright
  • Rob Goldin
  • Adrian V. S. Hill
  • Howard C. Thomas
  • Mark R. Thursz
Original Paper

DOI: 10.1007/s00251-003-0594-5

Cite this article as:
Knapp, S., Hennig, B.J.W., Frodsham, A.J. et al. Immunogenetics (2003) 55: 362. doi: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

Self-limiting infectionInterferonFibrosisGenotypeDisease associationHepatitis C

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Susanne Knapp
    • 1
  • Branwen J. W. Hennig
    • 2
  • Angela J. Frodsham
    • 2
  • Lyna Zhang
    • 2
  • Simon Hellier
    • 2
  • Mark Wright
    • 1
  • Rob Goldin
    • 1
  • Adrian V. S. Hill
    • 2
  • Howard C. Thomas
    • 1
  • Mark R. Thursz
    • 1
  1. 1.Faculty of Medicine, Imperial CollegeSt Mary's Hospital CampusLondonUK
  2. 2.Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK