Association between polymorphism of tumor necrosis factor-alpha promoter and response to lamivudine treatment in patients with chronic hepatitis B

Dig Dis Sci. 2010 Jul;55(7):2043-8. doi: 10.1007/s10620-009-0983-1. Epub 2009 Oct 15.

Abstract

Background: TNF-alpha promoter polymorphism is known to play an important role in the immunopathogenesis of infection of hepatitis B virus.

Aims: We investigated whether polymorphisms of TNF-alpha promoter at position -308 or -238 had associations with the response to lamivudine treatment.

Methods: A total of 89 healthy subjects (control group) and 225 patients with chronic hepatitis B treated with lamivudine were included in this study. Polymorphisms of TNF-alpha promoter at position -308 and -238 were analyzed by polymerase chain reaction. Recruited patients were classified according to the outcome of lamivudine treatment into the responder (103 patients) or non-responder (122 patients) group.

Results: The numbers of A allelic polymorphism of TNF-alpha promoter at position -238 were four (2.2%) in the control, five (2.4%) in the responder and 19 (7.8%) in the non-responder group. The A allele was noted significantly more frequently in the responder than non-responder group (P = 0.012). At position -308, a significant difference was observed between the control group (14; 7.9%) and total chronic hepatitis B patients (15; 3.3%) (P = 0.015).

Conclusions: Our study demonstrated that the non-response to lamivudine treatment in patients with chronic hepatitis B might be related to the A allelic polymorphism of TNF-alpha promoter at position -238.

Publication types

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

MeSH terms

  • Adult
  • Analysis of Variance
  • Case-Control Studies
  • Confidence Intervals
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation
  • Genotype
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Lamivudine / therapeutic use*
  • Liver Function Tests
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Polymorphism, Genetic*
  • Probability
  • Promoter Regions, Genetic / drug effects*
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Failure
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Tumor Necrosis Factor-alpha
  • Lamivudine