Interleukin-1, interleukin-10 and tumour necrosis factor-alpha gene polymorphisms in hepatitis C virus infection: an investigation of the relationships with spontaneous viral clearance and response to alpha-interferon therapy

Liver. 2002 Oct;22(5):404-12. doi: 10.1034/j.1600-0676.2002.01553.x.

Abstract

Background/aims: Though there is a consensus that the HLA DQB1*0301 allele is important in untreated HCV clearance, this association is not universal and a number of genes outside the major histocompatibility complex may also play a role in host responses to HCV infection. Prime candidates, at present, are the genes encoding pro-inflammatory and immuno-regulatory cytokines. The aim of this study was to investigate the relationship between a number of these candidate genes and both spontaneous and treatment related clearance of hepatitis C virus infection.

Methods: Three members of the interleukin-1 gene family: IL-1A, IL-1B and IL-1RN, three polymorphic sites in the interleukin-10 gene promoter (- 1082, - 819, - 592) and two in the tumour necrosis factor-alpha promoter (- 308, - 238) were studied in two independent DNA banks, each with appropriate controls. Standard PCR-based genotyping techniques were used.

Results: No significant difference in the distribution of any of the polymorphisms was found in either study set.

Conclusions: These findings in two large groups suggest that future investigations should focus on other candidate genes and may support the view that MHC-encoded susceptibility to chronic HCV infection may be determined by MHC class II rather than MHC class III genes.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cytokines / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / genetics
  • Hepatitis C, Chronic* / immunology
  • Hepatitis C, Chronic* / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interleukin-1 / genetics
  • Interleukin-10 / genetics
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • RNA, Viral / analysis
  • Tumor Necrosis Factor-alpha / genetics
  • Viral Load
  • Viremia / genetics*
  • Viremia / immunology

Substances

  • Cytokines
  • Interferon-alpha
  • Interleukin-1
  • RNA, Viral
  • Tumor Necrosis Factor-alpha
  • Interleukin-10