title: Frequency and clinical significance of core promoter and precore region mutations in Tunisian patients infected chronically with hepatitis B.
abstract: Genetic variability of hepatitis B virus (HBV) in the C gene and its association with the different stages of chronic liver disease has been studied inadequately with controversial results. The objectives of the current study were to determine the frequency of core promoter and precore mutations in chronic hepatitis B in Tunisia and to evaluate their impact on viral replication and disease progression. Sequencing was performed in upstream regulatory sequence (URS), pre-core (PreC) and basal core promoter (BCP) regions for 123 chronic infected patients by HBV genotype D at different status of disease. Mutations were detected in 98.4% of cases, affecting URS, BCP and Pre-C in 95.1%, 95.9% and 87.8% respectively. Multi-mutations increased significantly from asymptomatic carrier to advanced liver disease status. G1896A (74.8%), G1764A/T/C (71.5%), G1899A (54.4%) and T1678C (52%) were the most common. Special attention should be paid to A1703T, T1678C/G-A1703T, and A1652G-A1679G mutations probably specific of Tunisians sequences; they were observed in 40.6%, 41.5% and 30.1% respectively. A1679G/C, T1753C/G/A, A1762T/G and A1762T-G1764A were more prevalent in older patients. High DNA levels were associated with G1899A or G1764T/C-C1766G-C1799G and advanced liver disease with mutations at positions 1762, 1764 and/or 1899 alone or in double or triple mutations. It was also shown that substitutions at nucleotides 1762, 1764 and 1899 have an impact on the disease progression. It is the first report for specific mutations in the URS region for genotype D. It should be completed by studying eventual correlation with clinical progression and the response to treatment.
authors.affiliation: Laboratory of Clinical Virology, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: Rim
authors.initials: R
authors.lastname: Ouneissa
authors.forename: Olfa
authors.initials: O
authors.lastname: Bahri
authors.forename: Nissaf Ben
authors.initials: NB
authors.lastname: Alaya-Bouafif
authors.forename: Sofiene
authors.initials: S
authors.lastname: Chouaieb
authors.forename: Ahlem
authors.initials: A
authors.lastname: Ben Yahia
authors.forename: Amel
authors.initials: A
authors.lastname: Sadraoui
authors.forename: Walid
authors.initials: W
authors.lastname: Hammami
authors.forename: Noureddine
authors.initials: N
authors.lastname: Filali
authors.forename: Mohamed Msaddak
authors.initials: MM
authors.lastname: Azzouz
authors.forename: Nabyl Ben
authors.initials: NB
authors.lastname: Mami
authors.forename: Henda
authors.initials: H
authors.lastname: Triki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000473:pathology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014416:Tunisia; D014779:Virus Replication; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens