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Int J Clin Exp Pathol 2013;6(6):1076-1085

Original Article
Accumulation of the mutations in basal core promoter of hepatitis B virus subgenotype
C1 increase the risk of hepatocellular carcinoma in Southern China

Weihua Li, Guangyuan Chen, Xianwen Yu, Yongying Shi, Miaoguan Peng, Jianjun Wei

Department of Infectious disease, the First affiliated Hospital of Guangzhou Medical College, Guangzhou 510102, Guangdong Province, China;
Hepatitis Research Room, the First affiliated Hospital of Guangzhou Medical College, Guangzhou 510102, Guangdong Province, China

Received April 15, 2013; Accepted April 30, 2013; Epub May 15, 2013; Published June 1, 2013

Abstract: Hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC). In addition, HBV
subgenotype C1 is the major subgenotype in Southern China. The aim of this study was to investigate whether there was the specific mutation
patterns in HBV/C1 associated with Southern Chinese patients with HCC. Methods: Mutations in HBV basal core promoter (BCP) and their
association with HCC were assessed in a matched cross-sectional control study of 102 HCC and 105 chronic hepatitis (CH) patients (from
Guangdong, China) infected with HBV/C1. Functional analysis of HBx mutants was performed by the colony formation assay and the luciferase
assays. Results: T1762/A1764 double mutations was frequently found in patients infected with HBV/C1, regardless of clinical status (64.7% in
HCC and 51.4% in CH, P>0.05). Unexpectedly, the adjacent V1753 or A1768 mutation significantly increased the risk of HCC (P<0.05).
Moreover, the prevalence of triple or quadruple mutations in BCP was significantly higher in patients with HCC than those with CH, particularly
for HBeAg-positive-carriers (P<0.05). Functional analysis revealed that T1762/A1764 mutation alone did not alter the transcriptional activity and
the inhibitory effects on cell proliferation of HBx, but triple or quadruple mutations largely abrogated this effect. Conclusions: Accumulation of
mutations involving V1753 or/and A1768 in addition to T1762/A1764 in BCP region were closely related to HCC among the patients infected
with HBV/C1, particularly for HBeAg-positive-carriers. The increased risk of HCC caused by BCP variants may be attributable partially to
modifying the biological functions of HBx. (IJCEP1304022).

Keywords: Hepatitis B virus, basal core promoter, X gene, mutation, hepatocellular carcinoma

Address correspondence to: Dr. Wei-Hua Li, Department of Infectious disease, the First affiliated Hospital of Guangzhou Medical College,
Guangzhou 510102, China. Tel: 86-20-83062268; Fax: 86-20-83062245; E-mail: liweihuascu@163.com