Nucleotide change of codon 38 in the X gene of hepatitis B virus genotype C is associated with an increased risk of hepatocellular carcinoma.
OBJECTIVE
The hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC). In addition, the HBV X gene, which encodes the pleiotropic transactivator HBx, has also been associated with the development of HCC. In this study, we investigated whether nucleotide changes in the X gene of genotype C are associated with the development of HCC.


RESULTS
We sequenced the X gene in age- and sex-matched 39 HBV-infected patients with HCC and 36 HBV-infected patients without HCC. A novel nucleotide change that resulted in a proline to serine substitution at codon 38 in HBx (codon-38 change) was preferentially found in patients with HCC. Then, sera were collected from a new group of age- and sex-matched 52 patients with HCC and 51 patients without HCC. In this cohort also, the codon-38 change was associated with HCC. Multiple logistic regression analysis showed the prevalence of the codon-38 change was significantly associated with HCC in all patients (P=0.001, odds ratio: 4.89).


CONCLUSIONS
The codon-38 change in genotype C is an independent risk factor for the development of HCC and may serve as a useful molecular marker for predicting the clinical outcomes in patients infected with HBV.
Muroyama
Ryosuke
R
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Kato
Naoya
N
Yoshida
Haruhiko
H
Otsuka
Motoyuki
M
Moriyama
Masaru
M
Wang
Yue
Y
Shao
Run-Xuan
RX
Dharel
Narayan
N
Tanaka
Yasuo
Y
Ohta
Miki
M
Tateishi
Ryosuke
R
Shiina
Shuichiro
S
Tatsukawa
Masashi
M
Fukai
Kenichi
K
Imazeki
Fumio
F
Yokosuka
Osamu
O
Shiratori
Yasushi
Y
Omata
Masao
M
D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology; D003062:Codon; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006509:Hepatitis B / Q000150:complications* / Q000473:pathology / Q000821:virology; D006511:Hepatitis B Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009711:Nucleotides / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
D003062:Codon; D004279:DNA, Viral; D006511:Hepatitis B Antigens; D009711:Nucleotides; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein