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 infection and development of liver diseases. We analysed this region in Singaporean HBV carriers and assessed their association with viral replication and liver damage.


METHODS
Thirty-three Singaporean HBV carriers were selected. Serological markers for HBV infection and indicators for liver functions were analysed using commercial kits. Among these patients, 17 were chronic carriers, 10 had cirrhotic livers and 6 others had hepatocellular carcinoma (HCC). The region on the HBV genome covering the entire core promoter and core gene was amplified for each patient by polymerase chain reaction. The amplified 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 compared with the wild type sequences in patients with liver damage. Most mutations in either the core promoter or precore gene significantly reduced the viral 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 binding site of liver enriched factor, within the core promoter.


CONCLUSIONS
Our findings revealed a different mutation pattern in the core promoter in Singaporean HBV carriers. While most mutations may not be directly associated with the development of liver diseases, deletions in the core promoter could contribute to enhanced viral replication and should be studied further.
Chen
W N
WN
Singapore General Hospital, Republic of Singapore. gcrcwn@sgh.gov.sg
Oon
C J
CJ
D000328:Adult; D000368:Aged; D002353:Carrier State; D018388:Codon, Terminator / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006509:Hepatitis B / Q000208:ethnology / Q000473:pathology / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012846:Singapore; D014779:Virus Replication
D018388:Codon, Terminator