Nucleotide Variability of Core Promoter Region in Type B Chronic Liver Diseases

Kim, Yong Sung; Seo, Geom Suk; Song, Woo Gun; Kim, Haak Cheoul

Abstract

BACKGROUND/AIMS: The core promoter (CP) is included in X-gene of hepatitis B virus (HBV), and is composed of a upstream regulatory sequence (URS) and a basic core promotor (BCP) which is regulated by URS. Nucleotide (nt) mutation of CP might influence the expression of precore mRNA and pregenomic mRNA and the activity of liver disease. Thus, we investigated the relation between the nucleotide mutations in CP and their effects on HBeAg status, and severity of disease in chronic B viral liver disease.
METHODS
Samples were obtained from 7 chronic asymptomatic carriers, 9 patients with chronic hepatitis and 20 cirrhotic patients with HBV. Polymerase chain reaction and DNA analysis for CP were performed.
RESULTS
Cirrhotic group was older than asymptomatic carrier group and chronic hepatitis group. In BCP, point mutations were observed in 10 positions. Among them, nts 1753, 1762 and 1764 were frequently mutated, and the mutations at the nts 1762 and 1764 were accompanied (double mutation). In URS, point mutations were observed in 19 positions. Among these, nt 1653 (alpha-box) had significantly high mutation rate and the mutation at nt 1653 was closely associated with mutations at nts 1762/1764 in chronic liver disease and HBeAg (-) groups.
CONCLUSIONS
The alpha-box of URS is closely related with double-mutation in BCP and HBeAg status in chronic B viral liver disease.