Hepatitis B virus (HBV) genotypes/subgenotypes in China: mutations in core promoter and precore/core and their clinical implications.
BACKGROUND
The association of hepatitis B virus (HBV) genotypes with clinical course of infection is increasingly recognized.


OBJECTIVE
In order to investigate the genetic diversity of HBV and its clinical implications, 241 HBV-infected patients including 34 with hepatocellular carcinoma (HCC) were enrolled in this study.


METHODS
HBV genotyping was performed with an ELISA assay. HBV subgenotypes were determined by PCR-RFLP. HBV core promoter/precore/core mutations were analyzed by direct sequencing.


RESULTS
The overall prevalence of HBV/B and C was 65% and 33%, respectively. Among HBV/C, 42% were Cs/C1 and 58% were Ce/C2. The HBV/C1 was only found in the patients originating from Southern China (p=0.0001). Among HCC patients, HBV/C2 was only found in the elder age group (> or =51 years; p<0.05) and HBV/Ba was associated with young HCC patients (<35 years). Mutations associated with HCC were V1753 and T1762/A1764 (p<0.01). The prevalence of the V1753 was higher in HBV/C1 strains (p<0.04), A1898 was only found among HBV/C1 (p=0.056). T1762/A1764 was frequently demonstrated in both subgenotypes. The T1858 (90%) and A1896 (40%) mutations were most frequent in HBV/C2 (p<0.008).


CONCLUSIONS
HBV/C1 and HBV/C2 have distinct geographic distributions in China. V1753 in addition to T1762/A1764 double mutation in the basal core promoter region seems to be associated with HCC development, especially in the patients with HBV/C1.
Yuan
Jing
J
Shenzhen East Lake Hospital, Shenzhen, China.
Zhou
Boping
B
Tanaka
Yasuhito
Y
Kurbanov
Fuat
F
Orito
Etsuro
E
Gong
Zuojiong
Z
Xu
Liumei
L
Lu
Jian
J
Jiang
Xiaoling
X
Lai
Weizhen
W
Mizokami
Masashi
M
D000328:Adult; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000821:virology*; D002681:China; D004742:Enhancer Elements, Genetic; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011401:Promoter Regions, Genetic; D014758:Viral Core Proteins / Q000235:genetics*
D014758:Viral Core Proteins