乙型肝炎病毒C基因启动子和前C基因变异对HBeAg含量和HBVDNA定量及肝炎病情的影响

The Effects of Mutations in the Core Promoter and the Precore Gene of Hepatitis B Virus on Serum Content of e Antigen,Viral Replication and the Severity of Chronic Hepatitis B

目的 研究乙型肝炎病毒 (HBV)C基因启动子 (CP)和前C基因变异对HBeAg含量和HBVDNA定量及肝炎病情的影响。方法 通过DNA扩增、基因序列分析检测 75例慢性乙肝、 14例慢性重型乙肝和 34例肝硬化患者的血清HBVCP和前C基因序列 ,通过微粒子发光法定量检测血清中HBeAg的含量 ,通过荧光定量PCR技术检测血清HBVDNA含量。结果 (1)中度和重度慢性乙型肝炎 (CH)患者CP双变异 (nt176 2A→T和 176 4G→A)的发生率同轻度CH组比较显著升高 (分别为 6 1 3%和 6 1 1%VS 2 3 1% ) ;肝硬化组患者CP双变异发生率同CH组比较显著升高(76 5 %VS 4 8 0 % )。前C基因终止变异 (nt1896G→A)在重型乙型肝炎患者中的发生率显著升高 (71 4 % )。 (2 )双变异组和终止变异组患者HBeAg含量均显著下降 ,但后者下降更明显。双变异组的HBeAb阳性率和对照组比较无明显差异 ,但终止变异组的HBeAb阳性率同双变异组和对照组比较差异显著。终止变异联合双变异组的HBeAg含量及HBeAb阳性率同终止变异组相似。 (3)双变异组和对照组患者HBVDNA含量间无明显差异。结论 CP双变异和前C基因终止变异均影响HBeAg表达 ,但后者影响更大 ;在对病情影响上 ,前者与肝硬化发病有关 ,后者则与重型乙肝发病有关。

Objective To study the effects of mutations in the core promoter (CP) and the precore gene of hepatitis B virus ( HBV) on serum content of e antigen,viral replication and the severity of chronic hepatitis B.Methods CP and precore gene were sequenced directly from sera of 75 cases of patients with chronic hepatitis B(CH),14 cases of patients with chronic severe hepatitis B(CSH) and 34 cases of patients with liver cirrhosis,after application by the polymerize chain reaction.Results CP mutations in CP(A-to-T at nt 1762 and G-to- A at nt 1764)) were observed in 36 of 75 cases of patients with CH (48.0%),6 of 14 cases of patients with CSH(42.9%) and 26 of 34 cases of patients with liver cirrhosis(76.5%).There was significant difference in the prevalence of CP mutations with and without liver cirrhosis.Precore mutation(G-to- A at nt1896) were observed in 20 of 75 cases of patients with CH (26.7%) and in 10 of 14 cases of patients with CSH(71.4%),the difference of which was significant.Content of e antigen from sera of patients with CP mutations and /or precore mutation was significantly lower than that of patients without the mutations.But,patients with precore mutation significantly manifested HBeAg seroconversion.CP mutations did not significantly affect HBVDNA level.Conclusion Precore mutation and CP mutations decrease or block synthesis of HBeAg,and are related to the severity of chronic hepatitis B.