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

Baptista, Marina Da Conceicao Pinto Azevedo
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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.