乙型肝炎病毒C基因启动子区域T1762 A1764变异的临床及干扰素应答  

THE CORE PROMOTER MUTANT(T1762 A1764) OF HEPATITIS B VIRUS:CLINICAL SIGNIFICANCE AND ITS EFFECTS ON THE RESPONSE TO INTERFERON 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] 臧桂珍[1] 

机构地区：[1]南京市第二医院,南京210003

出　　处：《海南医学》2001年第10期81-83,共3页Hainan Medical Journal

基　　金：铁道部医学科研基金资助 (J99Z138)

摘　　要：目的　研究乙型肝炎病毒 (HBV)C基因启动子 (CP)区域T176 2A176 4变异与慢性乙型肝炎病情严重性及干扰素应答的关系。方法　通过聚合酶链反应 (PCR)及其产物直接测序 ,检测 4例无症状慢性HBV携带者 (AsC)、2 7例慢性乙肝病人血清的HBVCP序列 ,并定量检测病人血清的HBVDNA水平。结果　CPT176 2A176 4变异在慢性乙肝病人的发生率为 5 1.9% ( 14 2 7) ,更多的是在病情较重 (肝损害中度以上 )的病例中出现 (P <0 .0 5 ) ,且该变异株具有生存优势。干扰素治疗 3个月后 ,感染该优势变异株的慢性乙肝病人血清HBVDNA拷贝数下降 36 .6± 2 5 .1倍 ,显著高于非变异株病人 ( 2 .5± 2 .1倍 ) ;HBeAg阴转率 ( 75 % )及HBVDNA(斑点法 )阴转率 ( 77.8% )也显著高于对照组 ( 16 .7% ,16 .7% ) ;对 4例变异干扰素组病人 3个月后再次测序 ,有 3例其变异株的生存优势被野生株 (WT)替代。结论　HBVCPT176 2A176Objective: To investigate the clinical significance of the core promoter(CP) mutant(T1762A1764) of hepatitis B virus (HBV) and its effects on the response to interferon in patients with chronic hepatitis B (CHB).Methods: CP region were sequenced directly from sera of four cases of chronic asymptomatic HBV carriers(AsC) and twenty-seven patients with CHB,after amplication by the polymerase chain reaction(PCR).The content of serum HBV DNA was tested with quantitive PCR technique to evaluate the effectiveness of clinical antiviral treatment.Results: The double mutant was detected in 14 of 27 patients with CHB and the prevalence of mutant in patients with obvious liver damage was significantly higher than in patients with mild liver damage.The mutant viral strain prevailed over wild type one(WT) during survival.After α-interferon treatment,the amount of serum HBV DNA significantly declined and seroconversion rates of HBeAg positive to negative and HBV DNA positive to negative significanlty rised in CHB patients infected with dominant HBV strain with the double mutant as compared to controls.Resequencing showed that the dominant of the double mutant was replaced by WT in 3 out of 4 cases after interferon administration.Conclusion:HBV strain with the double mutant of nucleotides 1762 and 1764 in the CP seem to be more wensitive to α-interferon compared with WT.

关 键 词：乙型肝炎病毒 C基因启动子 基因变异 干扰素 免疫应答 肝损害 

分 类 号：R373.21[医药卫生—病原生物学] R394.8[医药卫生—基础医学]