[Detection of core promoter mutations in chronic hepatitis B]

To study the core promoter mutation in chronic hepatitis B and its effect on viral serology.

HBV core promoter gene fragments were amplified by using mismatched PCR combined with a restriction fragment length polymorphism assay. The PCR products were digested with Bcl I and subjected to electrophoresis on agarose gels.

We investigated the core promoter mutation in 89 patients with HBV DNA positive. The patterns of restriction fragment length polymorphism (RFIP) of the core promoter gene were distinguished and verified by direct sequencing. The combined mutations of nucleotides (nt) 1762 and 1764 in the core promoter from A to T and G to A were detected in 47 individuals, 21 of 43 HBeAg positive patients and 26 of 46 anti- HBe positive cases were found infected with this combined mutant. These two groups showed no significant difference (P > 0.05). The combined mutation was found in 11 of the 15 patients with medium and severe chronic hepatitis. In 5 chronic hepatitis B patients with coexistence of wild-type and mutant a tendency of superior accumulation of mutant was found.

This study suggests that the core promoter mutations commonly exist in Chinese chronic hepatitis B patients. The mutation can only reduce the pre-core mRNA transcribing efficiency, but cannot discontinue the synthesis of HBeAg. The effect on serology in this mutation is different from that in pre-core stop 28 mutation. The superior accumulation of mutations seems relating to the degree of chronic liver disease.