Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China.
Antiviral Res. 2012 Nov;96(2):108-14. doi: 10.1016/j.antiviral.2012.08.009. Epub 2012 Aug 31.
The present study was aimed to obtain baseline information of basal core promoter A1762T/G1764A and precore G1896A mutations of hepatitis B virus (HBV) in 192 HBeAg-positive chronically-infected Chinese patients, who were potential candidates for antiviral treatment. The detection of these mutations (including minor mutant subpopulations) was achieved by direct sequencing, whose sensitivity for minor mutant subpopulations identification was confirmed by clone sequencing. Patients enrolled were infected with either genotype B (46.35%) or C (53.65%) HBV identified by routine tests in our laboratory. The A1762T/G1764A or G1896A mutations were detected in 125specimens (125/192, 65.10%), in which 77 (77/125, 61.60%) existed as subpopulations. The A1762T/G1764A mutations were found to be more prevalent in genotype C than that in genotype B HBV [62.14% (64/103) vs. 20.22% (18/89), P<0.0001]. There is no statistically significant link between G1896A and genotypes. The emergence of A1762T/G1764A mutations was also found to be associated with an older age, an elevated ALT/AST level, and a lower HBsAg level in serum [wild-type vs. mutant: 4.57 (3.46-5.42) vs. 3.93 (2.51-5.36), P<0.0001]. In conclusion, HBV basal core promoter mutations A1762T/G1764A are associated with genotype C and a low serum HBsAg level in chronically-infected HBeAg-positive Chinese patients.
本研究旨在获得 192 例 HBeAg 阳性慢性感染中国患者乙型肝炎病毒(HBV)基本核心启动子 A1762T/G1764A 和前核心 G1896A 突变的基线信息,这些患者是抗病毒治疗的潜在候选者。通过直接测序检测这些突变(包括次要突变亚群),通过克隆测序证实了其检测次要突变亚群的灵敏度。入组患者感染的 HBV 基因型为 B(46.35%)或 C(53.65%),这是通过我们实验室的常规检测确定的。在 125 份标本(125/192,65.10%)中检测到 A1762T/G1764A 或 G1896A 突变,其中 77 份(77/125,61.60%)为亚群。A1762T/G1764A 突变在基因型 C 中比在基因型 B HBV 中更为常见[62.14%(64/103)比 20.22%(18/89),P<0.0001]。G1896A 与基因型之间没有统计学上的显著关联。还发现 A1762T/G1764A 突变的出现与年龄较大、ALT/AST 水平升高和血清 HBsAg 水平降低有关[野生型与突变型:4.57(3.46-5.42)比 3.93(2.51-5.36),P<0.0001]。总之,HBV 基本核心启动子突变 A1762T/G1764A 与慢性感染 HBeAg 阳性中国患者的基因型 C 和血清 HBsAg 水平较低有关。