title: Comparison of hepatitis B X gene mutation between patients with hepatocellular carcinoma and patients with chronic hepatitis B.
abstract: Hepatitis B virus (HBV), a major causative agent of hepatocellular carcinoma (HCC), encodes an oncogenic X protein (HBx) that transcriptionally activates multiple viral and cellular promoters. The present study aimed to identify the specific gene mutation related to the clinical outcome of HCC. Seventy-two HBV-infected patients (38 with chronic HBV infection and 34 with HCC) with well-characterized clinical profiles were enrolled. The HBx region was amplified from patient serum samples and analyzed by sequencing. Genotypes were determined using the National Center for Biotechnology Information genotype tool. All isolates were genotype B or C. Enhancer II nucleotide substitutions in the HCC group were significantly different from those in the chronic hepatitis B (CHB) group (Ρ < 0.05). HCC patients with genotype C had a higher risk of harboring the 1762/1764 double mutation than those with genotype B. The incidence of the 1762/1764 double mutation was higher in the high viral load group (>10(6) copies/ml) than in the low viral load group (≤10(6) copies/ml) (P = 0.03). The 1762/1764 double mutations may be related to the genotype and viral load. We found significantly more direct repeat sequence 1 (DR1) nucleotide substitutions in the HCC group (32.4%, 11/34) than in the CHB group (10.5%, 4/38) (Ρ < 0.05). Patients with higher viral load and genotype C had a higher incidence of 1762/1764 double mutations, which may not be related with development of HCC. Enhancer II and DR1 may play an important role in HCC development via nucleotide substitution.
authors.affiliation: Institute of Organ Transplantation, Chinese PLA Postgraduate Medical School, The No. 309th Hospital of PLA, Beijing, China. wenmei_fan@yahoo.com.cn
authors.forename: Wenmei
authors.initials: W
authors.lastname: Fan
authors.forename: Bingyi
authors.initials: B
authors.lastname: Shi
authors.forename: Hongshan
authors.initials: H
authors.lastname: Wei
authors.forename: Guosheng
authors.initials: G
authors.lastname: Du
authors.forename: Shujing
authors.initials: S
authors.lastname: Song
mesh_terms: D000328:Adult; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D004252:DNA Mutational Analysis; D004279:DNA, Viral; D004742:Enhancer Elements, Genetic; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016385:TATA Box; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D004279:DNA, Viral; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein