Mutations and deletions in core promoter and precore stop codon in relation to viral replication and liver damage in Singaporean hepatitis B virus carriers

Background The core promoter of hepatitis B virus (HBV) is crucial for the viral replication and mutations may lead to the establishment of chronic in fection and development of liver diseases. We analysed this region in Singa porean HBV carriers and assessed their association with viral replication a nd liver damage. Materials and Methods Thirty-three Singaporean HBV carriers were selected. Serological markers for HBV infection and indicators for liver functions we re analysed using commercial kits. Among these patients, 17 were chronic ca rriers, 10 had cirrhotic livers and 6 others had hepatocellular carcinoma ( HCC). The region on the HBV genome covering the entire core promoter and co re gene was amplified for each patient by polymerase chain reaction. The am plified DNA fragments were sequenced and analysed. Results The incidence of mutations in the core promoter or the precore gene product (stop codon at amino acid 28) was not significantly higher compare d with the wild type sequences in patients with liver damage. Most mutation s in either the core promoter or precore gene significantly reduced the vir al replication, as indicated by HBV DNA levels. High levels of HBV DNA were found in three mutants with deletion in the same region, presumably the bi nding site of liver enriched factor, within the core promoter. Conclusion Our findings revealed a different mutation pattern in the core p romoter in Singaporean HBV carriers. While most mutations may not be direct ly associated with the development of liver diseases, deletions in the core promoter could contribute to enhanced viral replication and should be stud ied further.