Mutations of X-gene in Chronic Hepatitis B Virus Carriers

Kim, Ji Woong; Song, Woo Kern; Kim, Haak Cheoul

Abstract

BACKGROUND/AIMS: X-gene product of hepatitis B virus (HBV) is known to cis-/trans-activate a number of cellular and viral promotors. We studied the mutations of X gene and investigated the relationship between the mutations and the severity of disease in chronic HBV carriers.
METHODS
HBV DNA samples were obtained from the sera of 11 chronic asymptomatic carriers (ASC group), 16 chronic hepatitis patients (CH group), and 23 cirrhotic patients with HBV (LC group). PCR and direct sequencing analysis were performed for X gene.
RESULTS
LC group was older than ASC group and CH group. In X gene, there were many mutation points and 17 hot-spots were found. Their variability was 1.17%. The mutations were not found in the direct repeat (DR) and TATA box binding portion (TBP), but hot-spots were found frequently in the 2nd TATA-box area, negative regulatory element (lNRE) and C/EBP. The nucleotide mutations occurred frequently at 1762 and 1764 nucleotide. The associated mutations at 1762 and 1764 nucleotide were accompanied by the mutation at one of 1653, 1613 and 1631 nucleotide. Even in those accompanied mutation, there were not interlinked between them, but has trend to cross-link between them.
CONCLUSIONS
DR and TBP portion in X gene might be an essential portion for HBV, and especially the 2nd TATA-box, NRE and C/EBP might be related to the severity of liver disease. Moreover there might be inter-, or cross-linked relationship between the mutations.