IL-10 promoter gene polymorphisms and sustained response to combination therapy in Taiwanese chronic hepatitis C patients

Dig Liver Dis. 2009 Jun;41(6):424-30. doi: 10.1016/j.dld.2008.09.017. Epub 2008 Nov 11.

Abstract

Background and aims: Host genetic factors may affect clinical outcomes of hepatitis C virus (HCV) infection; however, the possible mechanisms remain largely unknown. The role of immunopathogenesis in chronic hepatitis C leads to extensive exploration of host immunity including inflammatory cytokines.

Methods: We examined interleukin 10 (IL-10) promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site and studied their association with response to 24 weeks of pegylated interferon plus ribavirin treatment in 143 chronic hepatitis C patients, of whom 97 (67.8%) achieved a sustained virologic response (SVR). In addition, 134 healthy adults were used as controls.

Results: Of chronic hepatitis C patients, 111 (77.6%) were genotype 1 infection, 32 (22.4%) were genotype 2 infection. Patients with sustained virologic response were younger and had higher pretreatment ALT levels than those without. No statistical difference was found between chronic hepatitis C patients who achieved SVR or not in terms of gender, HCV genotype, pretreatment HCV RNA levels, and severity of liver disease. The serum IL-10 levels were comparable between healthy controls and chronic hepatitis C patients as well as between HCV patients with and without SVR. The distribution of IL-10 promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site was comparable between HCV patients and healthy controls as well as HCV patients with and without SVR. A high frequency of ATA haplotype of common IL-10 promoter gene SNPs was found in both chronic hepatitis C patients (70.3%) and healthy controls (69.8%). However, ATA haplotype was not associated with SVR in chronic hepatitis C patients.

Conclusions: Our data fail to demonstrate the influence of IL-10 promoter gene polymorphisms on the response to combination therapy in Taiwanese chronic hepatitis C patients. The impact of genetic variations in IL-10 haplotype on the response to anti-HCV treatment among different ethnic populations deserves further examination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Case-Control Studies
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Interleukin-10 / blood
  • Interleukin-10 / genetics*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic / genetics
  • Recombinant Proteins
  • Ribavirin / administration & dosage*
  • Taiwan
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • IL10 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Interleukin-10
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2b
  • peginterferon alfa-2a