乙型肝炎病毒基因型C亚型和核心启动子、前C/核心区基因变异的关系

目的 研究慢性乙型肝炎病毒（HBV）感染者中HBV基因型C亚型（HBV／C）的核心启动子、前C／核心区基因变异情况，分析HBV／C亚型的病毒学特征。方法 用酶联免疫法（ELISA）筛选出79例HBV／C，再用聚合酶链反应．限制性酶长度多态性分析方法（PCR-RFLP）进行HBV／C亚型分析；同时针对HBV核心启动子、DreC／核心区基因进行半巢式PCR及PCR产物直接测序。结果 ①79例HBV／C中，33例（41．8％）为HBV／C1亚型，46例（58．2％）为HBV／C2亚型。②HBV／C1亚型仅见于来自中国南方的患者（P〈0．0001）。③A1898位点变异仅见于HBV／C1亚型（P=0．056），V1753位点变异在HBV／C1亚型中多见（P〈0．05）；HBV／C2以T1858（90％）、A1896（40％）位点变异多见（P〈0．008）。T1762／A1764位点变异在HBV／C两种亚型中均常见。④肝细胞癌（HCC）患者中，V1753和T1762／A1764变异最常见（P〈0．05）。结论 HBV／CI和HBV／C2在中国有明显的地区差异；V1753合并T1762／A1764双变异与发展为HCC相关，尤其在HBV／C1患者。

Relationship between HBV/C subgenotypes and gene mutation of core promoter, precore/core region

Objective To study the core promoter, precore/core region mutation of HBV/C subgenotypes and to analyze the virological features. Methods A total of 79 sera of HBV/C genotype were chosen by the enzyme-linked immunosobent assay (ELISA). Then HBV/C strains were subtyped by polymerase chain reactioin and restricion fragment length polymporphism (PCR-RFLP), and their HBV DNA sequences bearing the core promoter, precore/core region were amplified by hemi-nested PCR, products thereof were directly sequenced. Results (1) Among 79 sera of HBV/C, 33 (41.8%) of subtype HBV/C1 and 46 (58.2%) of subtype HBV/C2 were detected. (2)The HBV/C1 was found only in patients from Southern China. (3) Prevalence of V1753 was higher in HBV/C1 strains (P<0.04), A1898 was only found among HBV/C1. HBV/C2 distinguished by frequently found T1858 (90%) and A1896 (40%). T1762/A1764 was frequent in both subgenotypes. (3) Mutations associated with HCC in the present study were V1753 and T1762/A1764. Conclusions HBV/C1 and HBV/C2 have distinct geographic distribution in China. V1753 in addition to T1762/A1764 double mutation would be associated with HCC development, especially among patients with HBV/C1.