title: Nucleotide mutations associated with hepatitis B e antigen negativity.
abstract: One hundred and forty four patients with chronic hepatitis B were tested to identify new mutations associated with hepatitis B e antigen (HBeAg) negativity, using a full genome sequence analysis. All the patients were Chinese and had hepatitis B virus infection of genotype C. Patients with none of the pre-core or core promoter mutations were significantly (P < 0.001) less common in the group with anti-HBe (13%) than in the group with HBeAg (56%). The complete nucleotide sequence was determined in four anti-HBe-positive patients who had neither pre-core nor core promoter mutations and in five HBeAg-positive patients who also had neither of these mutations (the groups were matched for age and sex). Six mutations were found to be significantly more common in the former group than in the latter: G529A (3/4 vs. 0/5), C934A (4/4 vs. 1/5), A1053G (4/4 vs. 1/5), G1915T/A (4/4 vs. 0/5), T2005C/A (4/4 vs. 0/5), and C3026T (3/4 vs. 0/5). Three of the six mutations were significantly more common in the four anti-HBe-positive patients who had neither pre-core nor core promoter mutations, compared to 11 HBeAg-positive patients who had pre-core and core promoter mutations, and also compared to 15 anti-HBe-positive patients who had pre-core and core promoter mutations, suggesting further the specificity of these mutations. Of the six mutations, two resulted in amino acid substitution in the polymerase protein, and one is located near the enhancer I region. The results suggest that the six newly discovered mutations are associated with HBeAg negativity.
authors.affiliation: Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: XiaoHong
authors.initials: X
authors.lastname: Sun
authors.forename: Akinori
authors.initials: A
authors.lastname: Rokuhara
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Amal
authors.initials: A
authors.lastname: Gad
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Mutou
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Kaname
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Kendo
authors.initials: K
authors.lastname: Kiyosawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D005260:Female; D006513:Hepatitis B e Antigens / Q000096:biosynthesis / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D017422:Sequence Analysis, DNA
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens