Nucleotide change of codon 182 in the surface gene of hepatitis B virus genotype C leading to truncated surface protein is associated with progression of liver diseases

J Hepatol. 2012 Jan;56(1):63-9. doi: 10.1016/j.jhep.2011.06.028. Epub 2011 Aug 7.

Abstract

Background & aims: Hepatitis B virus (HBV) genotype C infection is associated with progression of hepatocellular carcinoma (HCC). Specific mutations of the HBV surface (S) gene have been reported to contribute to the development of HCC. In this study, novel nucleotide changes (sW182*) that result in a premature stop at codon 182 in the S gene of genotype C are investigated with regards to the development of HCC.

Methods: A multi-probe real time PCR that enables rapid and reliable detection of sW182* was developed and applied to 292 DNA samples from Korean patients with diverse chronic liver diseases.

Results: sW182* was detected in a total of 73 patients out of the 275 with positive amplification (26.5%). Its prevalence was significantly higher in patients with progressive forms of the disease (HCC and liver cirrhosis) than in patients with less severe forms of the disease (chronic hepatitis and carrier) [31.8% (56/176 patients) vs. 17.2% (17/99 patients); p=0.010]. In addition, an in vitro study using cell lines stable expressing the S protein with sW182* also strongly supported its relationship with HCC.

Conclusions: In the present study, we demonstrate that the sW182* of HBV could provide an important contribution to the progression of liver diseases, through molecular epidemiologic and in vitro studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / etiology
  • Cell Line
  • Cell Proliferation
  • Codon, Nonsense*
  • DNA Primers / genetics
  • DNA, Viral / genetics
  • Disease Progression
  • Gene Expression
  • Genes, Viral*
  • Genes, cdc
  • Genotype
  • HEK293 Cells
  • Hepatitis B virus / classification
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / pathogenicity
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / virology*
  • Humans
  • Liver Neoplasms / etiology
  • Mice
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Sequence Homology, Nucleic Acid
  • Viral Proteins / genetics

Substances

  • Codon, Nonsense
  • DNA Primers
  • DNA, Viral
  • Viral Proteins