一种新发现的乙型肝炎病毒基因变异,C基因启动子nt1726-1730聚集变异及其可能的临床意义  

A kind of new-found mutation of hepatitis B virus,clustering mutations in nt 1726-1730 of the core promoter and its clinical significance in patients with chronic hepatitis B

作　　者：张汉荣[1] 刘新钰[1] 钟备[1] 方之勋[1] 赵巍[1] 

机构地区：[1]东南大学医学院附属南京第二医院,江苏南京210003

出　　处：《东南大学学报（医学版）》2001年第4期216-219,共4页Journal of Southeast University(Medical Science Edition)

基　　金：铁道部科技基金资助项目 (J99Z1 38)。

摘　　要：目的 :研究乙型肝炎病毒 (HBV)C基因启动子 (CP)变异与无症状慢性HBV携带者 (AsC)肝炎发作及慢性乙肝病情严重性的关系。方法 :通过PCR及其产物直接测序 ,检测 4例AsC、2 7例慢性乙肝和 3例慢性重型乙肝病人血清的HBVCP和前C/C基因序列 ,并定量检测病人血清的HBVDNA。结果 :( 1)CP主要变异除核苷酸 (nt) 176 2 176 4双变异( 176 2A→T和 176 4G→A)外 ,还存在nt172 6 1730聚集变异 ( 172 6A→C、172 7A→T、1730C→G)。 ( 2 ) 11例首次急性发作的慢性乙肝病人中 (既往均有AsC史 ) ,8例出现CP聚集变异。而 5例隐匿起病的慢性乙肝病人和 4例AsC无一例出现该变异 ,且 1例在AsC状态时无CP变异 ,肝炎发作时出现CP聚集变异。 ( 3)CP聚集变异合并CP双变异的乙肝病人 ,临床上或表现为重型肝炎或迅速进展为活动性肝硬变 ,HBVDNA水平高滴度 ,HBVDNA(斑点法 )阳性 ,HBeAg/抗HBe转换。结论 :CP聚集变异与AsC肝炎急性发作有关 ;CP聚集变异与CP双变异同时存在 。Objective To study the effects of mutations in the core promoter (CP) and the precore/core gene of hepatitis B virus ( HBV) on acute clinical exacerbation in chronic asymptomatic HBV carriers(AsC) and the severity of chronic hepatitis B.Methods CP and precore/core gene were sequenced directly from sera of four AsCs,twenty seven patients with chronic hepatitis B and three patients with chronic severe hepatitis B,after amplification by the polymerase chain reaction.Results (1)The mutations in CP region consisted of the double mutations(1726 A→T and 1764 G→A) and the clustering mutations(1726 A→C,1727 A→T,1730 C→G).(2)Clustering mutations in CP associated with AsC developing acute exacerbation.They were observed in eight of eleven AsC developing acute exacerbation,while five patients with chronic hepatitis B with obscure signs and four AsC had no clustering mutations in CP.Moreover,the clustering mutations were found negative in the state of AsC and positive after acute exacerbation in a subject.(3)The patients with both the clustering mutations and the double mutations manifested severe hepatitis or active cirrhosis with high level of serum HBV DNA, HBV DNA positive by dot blot,HBeAg negative and Anti HBe positive in serum.Conclusion The clustering mutations in CP region are associated with acute exacerbation in AsC,and co existence of the clustering mutations and the double mutations is related to the severity of chronic hepatitis B.

关 键 词：乙型肝炎病毒 C基因启动子 变异 聚合酶链反应 

分 类 号：R512.62[医药卫生—内科学]