Hepatitis B virus (HBV) genotypes/subgenotypes in China: mutations in core promoter and precore/core and their clinical implications

J Clin Virol. 2007 Jun;39(2):87-93. doi: 10.1016/j.jcv.2007.03.005. Epub 2007 Apr 23.

Abstract

Background: The association of hepatitis B virus (HBV) genotypes with clinical course of infection is increasingly recognized.

Objectives: In order to investigate the genetic diversity of HBV and its clinical implications, 241 HBV-infected patients including 34 with hepatocellular carcinoma (HCC) were enrolled in this study.

Methods: HBV genotyping was performed with an ELISA assay. HBV subgenotypes were determined by PCR-RFLP. HBV core promoter/precore/core mutations were analyzed by direct sequencing.

Results: The overall prevalence of HBV/B and C was 65% and 33%, respectively. Among HBV/C, 42% were Cs/C1 and 58% were Ce/C2. The HBV/C1 was only found in the patients originating from Southern China (p=0.0001). Among HCC patients, HBV/C2 was only found in the elder age group (> or =51 years; p<0.05) and HBV/Ba was associated with young HCC patients (<35 years). Mutations associated with HCC were V1753 and T1762/A1764 (p<0.01). The prevalence of the V1753 was higher in HBV/C1 strains (p<0.04), A1898 was only found among HBV/C1 (p=0.056). T1762/A1764 was frequently demonstrated in both subgenotypes. The T1858 (90%) and A1896 (40%) mutations were most frequent in HBV/C2 (p<0.008).

Conclusions: HBV/C1 and HBV/C2 have distinct geographic distributions in China. V1753 in addition to T1762/A1764 double mutation in the basal core promoter region seems to be associated with HCC development, especially in the patients with HBV/C1.

MeSH terms

  • Adult
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / virology*
  • China
  • Enhancer Elements, Genetic
  • Female
  • Genetic Variation
  • Genotype
  • Hepatitis B / epidemiology
  • Hepatitis B / immunology
  • Hepatitis B / physiopathology
  • Hepatitis B / virology*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology
  • Hepatitis B virus / isolation & purification
  • Hepatitis B virus / pathogenicity
  • Humans
  • Liver Neoplasms / immunology
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Prevalence
  • Promoter Regions, Genetic*
  • Viral Core Proteins / genetics*

Substances

  • Viral Core Proteins