Nucleotide Variability in Enhancer 1 and Pre-X Promotor Regions of Hepatitis B Virus from Patients with Chronic Hepatitis B Virus Infection

Song, Woo Kern; Kim, Haak Cheoul; Park, Do Sim; Cho, Ji Hyun

Abstract

BACKGROUND/AIMS: Hepatitis B Virus (HBV) is a compact DNA virus with four genes which are controlled by 6 promotors and two enhancers during its replication. However, HBV has variability in its nucleotide sequence and thus, it can be classified into genotypes. Recently, it is suggested that nucleotide mutations in its sequence are related to chronic liver disease (CLD). Therefore, we analyzed relationships between mutations and disease severity in its Enh 1 and X-promoter regions (1021-1373). METHODS: HBV DNA of the patients with chronic hepatitis (CH, n=30), liver cirrhosis (LC, n=25), and hepatocellular carcinoma (HCC, n=17) was amplified and sequenced. Then, we constructed a phylogenetic tree (PAUP4.0) and analyzed their mutation rates and specificity among the disease groups. RESULTS: All analyzed sequences belonged to genotype C. The divergency rate was 1.71% and there was no difference in their mutation rates, but there were some hot-spots among the disease groups. The hot-spots were at nucleotides 1317, 1229, 1126, 1134, and 1041 in decreasing order. Between the groups of LC and HCC, there were higher mutation rates at nucleotides 1126 (A->C) and 1134 (T->C) in LC, and at nucleotides 1229 (G->A) and 1317 (A->G) in HCC. The mutations at nucleotides 1126 and 1134 (p<0.001) were accompanied. CONCLUSIONS: The genotype of HBV in Korea is type C in all cases and there might exist the associated mutations and hot-spots related to CLD severity in Enh 1 and X-promoter regions.