Laboratory of Clinical Virology, Institut Pasteur de Tunis, Tunis, Tunisia.
J Med Virol. 2012 Nov;84(11):1719-26. doi: 10.1002/jmv.23394.
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.
乙型肝炎病毒 (HBV) C 基因的遗传变异性及其与慢性肝病不同阶段的关系研究不足，结果存在争议。本研究的目的是确定突尼斯慢性乙型肝炎患者核心启动子和前核心区突变的频率，并评估其对病毒复制和疾病进展的影响。对 123 例不同疾病状态的乙型肝炎病毒基因型 D 慢性感染者的上游调控序列 (URS)、前核心 (PreC) 和基本核心启动子 (BCP) 区进行测序。在 98.4%的病例中检测到突变，分别影响 URS、BCP 和 Pre-C 的发生率为 95.1%、95.9%和 87.8%。多突变从无症状携带者到晚期肝病的发生率显著增加。G1896A（74.8%）、G1764A/T/C（71.5%）、G1899A（54.4%）和 T1678C（52%）最为常见。特别注意 A1703T、T1678C/G-A1703T 和 A1652G-A1679G 突变，它们可能是突尼斯序列特有的；它们分别在 40.6%、41.5%和 30.1%的病例中观察到。A1679G/C、T1753C/G/A、A1762T/G 和 A1762T-G1764A 在年龄较大的患者中更为常见。高 DNA 水平与 G1899A 或 G1764T/C-C1766G-C1799G 相关，而 1762、1764 和/或 1899 位的突变与单一或双重或三重突变与晚期肝病相关。还表明，核苷酸 1762、1764 和 1899 的替换对疾病进展有影响。这是基因型 D 中 URS 区域特定突变的首次报道。应通过研究与临床进展和治疗反应的相关性来进一步完善。
