Nucleic acid sequence analysis of the distal X gene region containing the basic core promoter of the hepatitis B virus in southern African asymptomatic carriers of the virus and hepatocellular carcinoma patients
Date
2014-03-07
Authors
Baptista, Marina Da Conceicao Pinto Azevedo
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Abstract
The purpose of this study was to identify mutations in the basic core promoter and
enhancer II region a* the hepatitis B virus (HBV) that might result in the hepatitis B virus
e antigen (HBeAg)-negative phenotype and contribute to hepatocarcinogenesis in black
African carriers of the virus. The basic core promoter/enhancer II overlaps the X gene.
HBV DNAfrom serum of 47 asymptomatic carriers and 50 patients with hepatocellular
carcinoma and from 29 tumorous and 10 nontumorous liver tissues was amplified and
sequenced directly. That part of the enhancer II region not overlapping the basic core promoter was reasonably well conserved in all samples. Missense mutations at
positions 1809 and 1812 were found in 80% of all sequences and may represent
wiidtype sequence in southern African isolates. Nucleotide and amino acid divergences
were higher in the basic core promoter of hepatocellular carcinoma patients than of
asymptomatic carriers (p<0.0001). This applied particularly to the paired 1762 adenine
to thymine (1762T) and 1764 guanine to adenine (1764*) missense mutations, the prevalence of which was 66% in patients with hepatocellular carcinoma compared with
11% in asymptomatic carriers (p<0.0001). There was no association between the presence of 1762T1764A and the rate of HBeAg negativity, although these mutations
suppressed HBeAg titres in HBeAg-positive patients. Suppression of HBeAg expression
as well as alteration of amino acid sequence of the X protein may be contributing factors
in the development of hepatocarcinogenesis.