Cytokine gene polymorphisms in Japanese patients with hepatitis B virus infection--association between TGF-beta1 polymorphisms and hepatocellular carcinoma

J Hepatol. 2005 Apr;42(4):505-10. doi: 10.1016/j.jhep.2004.11.026. Epub 2004 Dec 10.

Abstract

Background/aims: In this study, we determined the frequencies of the genotypes associated with the polymorphism of the cytokines genes, and investigated their association with the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) carriers.

Methods: Genetic polymorphism in the cytokines TNF-alpha, IFN-gamma, TGF-beta1, IL-6, and IL-10 were studied in 236 Japanese patients with HBV infection. The genetic polymorphisms of these cytokines were analyzed by polymerase chain reaction-sequence-specific primer (SSP).

Results: There was no statistically significant difference in the genetic polymorphisms of TNF-alpha, IFN-gamma, and IL-10 genes between HBV carriers with HCC and those without HCC. However, the TGF-beta1+29 (codon 10) C/C genotype was lower in HBV carriers with HCC than in those without HCC (HCC 14.6% vs non-HCC 31.9%). The association of HCC was significantly lower in HBV carriers with C/C genotype than in those with T/C or T/T genotype in position +29 of the TGF-beta1 gene.

Conclusions: Our findings suggest that the genetic polymorphism in codon 10 of the TGF-beta1 gene may play a role in HCC development in patients with chronic HBV infection.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Codon
  • Female
  • Genotype
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Interleukin-6 / genetics
  • Japan
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Codon
  • Interleukin-6
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma