乙型肝炎病毒前S基因变异与肝病进展的关系  

The relationship between hepatitis B virus pre-S gene mutations and progression of liver disease

作　　者：丁静娟[1] 王梅[1] 刘悦晖[1] 

机构地区：[1]贵阳医学院附属医院感染科,550004

出　　处：《中华传染病杂志》2007年第6期332-337,共6页Chinese Journal of Infectious Diseases

基　　金：国家自然科学基金(30360098);贵州省优秀科技教育人才省长基金(黔省专合2005-71号)

摘　　要：目的探讨HBV前S基因变异与疾病进展的关系。方法收集无症状携带者（ASC）、慢性肝炎（CH）、肝炎肝硬化（LC）、肝细胞癌（HCC）患者血清138份，PCR扩增前S区基因．聚合酶链反应-限制性片段长度多态性检测前S2起始码变异，聚丙烯酰胺凝胶电泳（PAGE）分析前S缺失变异，直接测序确定前CA1896、基本核心启动子（BCP）T1762／A1764变异。数据行X^2检验。结果HCC、LC组前S缺失变异检出率分别为56．3％和42．9％，高于CH组的11．8％和ASC组的8．1％（P〈0．01）。前S2起始码变异检出率在HCC（50．0％）、LC（37．1％）组亦较CH（5．9％）、ASC（0）组高。前S缺失、前S2起始码变异在HBeAg阴性组的检出率分别为37．5％和36．1％，高于HBeAg阳性组的19．7％和7．6％（P〈0．01）。分析前S基因、T1762／A1764、A1896单独或联合变异在HCC、LC组和CH、ASC组的分布，Fisher精确检验表明，T1762／A1764和前S基因的联合变异是影响疾病进展、导致严重肝病的重要因素（P-0）。结论严重肝病患者前s基因变异发生率高，有T1762／A1764联合前S基因变异HBV感染者的肝病易进展。Objective To study the relationship between hepatitis B virus（HBV）pre-S gene mutations and progression of liver disease. Methods The entire pre-S1, pre-S2 genes were amplified by nested polymerase chain reaction（PCR） and the products were digested by Nla Ⅲ. The method for detecting pre-S2 start codon mutation was established based on the digested restriction fragment length polymorphism（RFLP）. Pre-S gene deletion was revealed by electrophoresis on polyacrylamide gel（PAGE）. Pre-C A1896 and basic core promoter T1762/A1764 mutations were identified by direct sequencing of PCR products. The 138 sera from patients with HBV-related disease, including asymptomatic carriers （ASC）, chronic hepatitis（CH）, liver cirrhosis （LC）, hepatocarcinoma （HCC）, were tested by these methods. Results The detection rate of pre-S deletion mutation was higher in patients with HCC（56.3%） and LC（42.9%） than those with CH（ll. 8%） and ASC（8.1%, P〈0.01）. The detection rate of pre-S2 start codon mutation was significantly higher in HCC（ 50. 0%） and LC （37.1% ） than CH （5.9 % ） and ASC（0, P % 0.01 ）. The detection rates of pre-S deletion and pre-S2 start codon mutations were higher in HBeAg negative patients than in HBeAg positive ones（37.50/00 vs 19.7%, 36. l%vs 7. 6% respectively） with significant difference（P 〈 0.01）. The distribution of either single mutation or combined T1762/A1764, A1896 and pre-S gene mutations between HCC ＋LC and CH ＋ ASC was analyzed by Fisher exact test. Combination of mutations, especially T1762/ A1764 combined with pre-S gene mutations, rather than single mutation was associated with the development of liver disease （P=0）. Conclusions The pre-S gene mutations are common in patients with severe liver disease. Patients with HBV harbouring both T1762/A1764 and pre-S gene mutations are more likely to have progressive liver diseases.

关 键 词：肝炎病毒 乙型 蛋白质前体 变异(遗传学) 多态性 限制性片段长度 序列 分析 肝疾病 

分 类 号：R512.6[医药卫生—内科学] R575.2[医药卫生—临床医学] R735.7