Frequency and clinical significance of core promoter and precore region mutations in Tunisian patients infected chronically with hepatitis B
| Autor: | Mohamed Msaddak Azzouz, Nabyl Ben Mami, Henda Triki, Noureddine Filali, Olfa Bahri, Rim Ouneissa, Ahlem Ben Yahia, Nissaf Ben Alaya-Bouafif, Walid Hammami, Amel Sadraoui, Sofiene Chouaieb |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Hepatitis B virus Tunisia Adolescent Genotype Molecular Sequence Data Biology Chronic liver disease medicine.disease_cause Virus Replication Liver disease Young Adult Hepatitis B Chronic Virology medicine Humans Promoter Regions Genetic Gene Aged Aged 80 and over Mutation Polymorphism Genetic Sequence Analysis DNA Hepatitis B Middle Aged medicine.disease Hepatitis B Core Antigens Infectious Diseases DNA Viral Disease Progression Female Asymptomatic carrier |
| Zdroj: | Journal of medical virology. 84(11) |
| ISSN: | 1096-9071 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text