Mutations in the basic core promoter region of hepatitis B virus. Relationship with precore variants and HBV genotypes in a Spanish population of HBV carriers.
OBJECTIVE
To determine the prevalence and significance of hepatitis B virus (HBV) basic core promoter (BCP) mutations and to establish their relationship with precore (preC) mutations, HBV genotypes and HBV-DNA levels.


METHODS
BCP and preC mutations and genotypes were determined by sequencing.


RESULTS
Genomic analysis was performed in 129 (71%) of 182 patients. BCP mutations were detected in 83% of 18 HBeAg-negative (e-) chronic hepatitis B (CHB) patients with fluctuating ALT levels, and in 76% of 58 e- CHB with elevated ALT. The prevalence was lower and similar, 55% in 30 HBeAg-positive CHB (e+ CHB) with elevated ALT and in 23 e- inactive carriers. Frequency of preC mutations was higher in e- CHB (80%) than in e- inactive carriers (65%). Among e- CHB, patients with elevated ALT and preC mutations at nt 1896 showed highest HBV-DNA, regardless of BCP mutations. BCP mutations were similar in genotypes A and D, while preC mutations were most common in genotype D (82 vs. 40%). Simultaneous presence of the main BCP (1762, 1764) and preC (1896, 1899) mutations was associated with the degree of histological injury.


CONCLUSIONS
Combined BCP and preC mutational and genotype analysis provides clinically relevant information in the study of HBV infection.
Jardi
Rosendo
R
Department of Biochemistry, Hospital Universitario Vall d'Hebron, Paseo Vall d'Hebron 119-129, Barcelona 08035, Spain. rjardi@hg.vhebron.es
Rodriguez
Francisco
F
Buti
Maria
M
Costa
Xose
X
Valdes
Auristela
A
Allende
Helena
H
Schaper
Melanie
M
Galimany
Roman
R
Esteban
Rafael
R
Guardia
Jaime
J
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D013030:Spain; D014758:Viral Core Proteins / Q000235:genetics*; D014779:Virus Replication
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D014758:Viral Core Proteins; D000410:Alanine Transaminase