Polymorphism in tumor necrosis factor-related apoptosis-inducing ligand receptor 1 is associated with poor viral response to interferon-based hepatitis C virus therapy in HIV/hepatitis C virus-coinfected individuals

AIDS. 2010 Nov 13;24(17):2639-44. doi: 10.1097/QAD.0b013e32833eacfd.

Abstract

Objective(s): HIV/hepatitis C virus (HCV) coinfection causes accelerated liver disease compared to HCV monoinfection, and only 30-60% of HIV/HCV-coinfected individuals respond to HCV therapy with pegylated interferon and ribavirin. There are currently no biomarkers that predict treatment response in these coinfected patients.

Design: We investigated whether there is an association between HCV treatment response and SNPs of apoptosis-related genes during HIV/HCV coinfection.

Method: Genomic DNA from 53 HIV/HCV-coinfected individuals was analyzed for 82 SNPs of 10 apoptosis-related genes.

Results: We found that the presence of the rs4242392 SNP in tumor necrosis factor receptor superfamily, member 10a (TNFRSF10A), which encodes for tumor necrosis factor-related apoptosis-inducing ligand receptor 1, predicts poor outcome to HCV therapy, in HIV/HCV-co-infected patients [odds ratio 5.91 (95% confidence interval 1.63-21.38, P = 0.007)].

Conclusion: The rs4242392 SNP of the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 gene predicted poor interferon-based HCV treatment response in HIV/HCV-coinfected patients.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects*
  • Canada
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects*
  • Liver Diseases / drug therapy*
  • Liver Diseases / virology
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • RNA, Viral
  • Receptors, Tumor Necrosis Factor, Member 25 / genetics*
  • Recombinant Proteins
  • Ribavirin / administration & dosage
  • Ribavirin / adverse effects*

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Receptors, Tumor Necrosis Factor, Member 25
  • Recombinant Proteins
  • Ribavirin