title: 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.
abstract: 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.
authors.affiliation: Department of Biochemistry, Hospital Universitario Vall d'Hebron, Paseo Vall d'Hebron 119-129, Barcelona 08035, Spain. rjardi@hg.vhebron.es
authors.forename: Rosendo
authors.initials: R
authors.lastname: Jardi
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Xose
authors.initials: X
authors.lastname: Costa
authors.forename: Auristela
authors.initials: A
authors.lastname: Valdes
authors.forename: Helena
authors.initials: H
authors.lastname: Allende
authors.forename: Melanie
authors.initials: M
authors.lastname: Schaper
authors.forename: Roman
authors.initials: R
authors.lastname: Galimany
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.forename: Jaime
authors.initials: J
authors.lastname: Guardia
mesh_terms: 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
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D014758:Viral Core Proteins; D000410:Alanine Transaminase