Longitudinal study on mutation profiles of core promoter and precore regions of the hepatitis B virus genome in children.
Precore nucleotide 1896 and core promoter mutations may account for hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B virus (HBV) infection, yet the mutational profiles of the core promoter are largely unknown in children. An age-matched, case-control study enrolled 110 chronic HBV-infected children, including 55 HBeAg seroconverters and 55 nonseroconverters. Precore and core promoter genes of HBV were sequenced and the serum viral genomes were genotyped from three serial serum samples of the seroconverters and from one serum sample of the nonseroconverters. Higher frequency of A1775G and G1799C mutation rates and lower frequency of A1752G mutation rate were found in the seroconverters. Precore 1896 mutation appeared more in seroconverters than in nonseroconverters (45.5% versus 10.9%; p < 0.001). 1762 + 1764 mutation rates were not different between the seroconverters (9.1%) and the nonseroconverters (5.5%). Genotype B was the major type. Genotype C was associated with core promoter 1762 + 1764 mutations in the seroconverter group (p = 0.023). The conclusions of this study include the following: 1) mutations of core promoter at nucleotide position 1752, 1775, and 1799 have significant correlations with HBeAg seroconversion; 2) core promoter 1762 + 1764 mutations play a minimal role in HBeAg seroconversion; 3) precore 1896 mutant accounted for half of childhood HBeAg seroconversion; 4) genotype C is associated with 1762 + 1764 mutations during the process of HBeAg seroconversion.
Ni
Yen-Hsuan
YH
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taiwan.
Chang
Mei-Hwei
MH
Hsu
Hong-Yuan
HY
Tsuei
Daw-Jen
DJ
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic; D006801:Humans; D008137:Longitudinal Studies; D009154:Mutation; D011401:Promoter Regions, Genetic
D006513:Hepatitis B e Antigens