Tumour necrosis factor-α promoter region polymorphisms affect the course of spontaneous HBsAg clearance

Liver Int. 2010 Nov;30(10):1448-53. doi: 10.1111/j.1478-3231.2010.02340.x. Epub 2010 Sep 1.

Abstract

Background: This study aimed to investigate the roles of tumour necrosis factor-α (TNF-α) gene polymorphisms in the spontaneous clearance of HBsAg after a hepatitis B virus (HBV) infection.

Methods: Polymorphisms in the TNF-α (-1031 T to C, -863 C to A, -857 C to T, -308 G to A and -238 G to A transition) gene were evaluated in 274 chronic HBV-infected patients and 194 patients with resolved HBV infection. The peripheral blood mononuclear cells (PBMC) isolated from 77 (28%) of the 274 chronic HBV-infected patients with negative HBeAg and positive antibody to HBeAg were stimulated with HBcAg. Data on TNF-α genotypes and phenotypes in subjects with/without the A allele at the TNF-α-863 promoter single nucleotide polymorphism (rs1800630) were compared.

Results: The A allele in the -863 promoter region of the TNF-α gene was present in 154 (56.2%) chronic HBV-infected patients and 87 (44.8%) patients who recovered from HBV infection (odds ratio 1.58; P<0.01). The TNF-α-863 A allele genotype predicted lower TNF-α production by PBMC after in vitro HBcAg stimulation (P<0.02).

Conclusions: The A allele at the -863 locus of the promoter region of the TNF-α gene predicts lower HBcAg-inducible TNF-α secretion. It is also associated with chronicity of HBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Cells, Cultured
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Hepatitis B / diagnosis
  • Hepatitis B / genetics*
  • Hepatitis B / immunology
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Linkage Disequilibrium
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Proportional Hazards Models
  • Remission, Spontaneous
  • Risk Assessment
  • Risk Factors
  • Taiwan
  • Tumor Necrosis Factor-alpha / genetics*
  • Young Adult

Substances

  • Biomarkers
  • Hepatitis B Surface Antigens
  • Tumor Necrosis Factor-alpha