958例乙型肝炎患者HBV前C/BCP区变异检测及其意义分析  

Mutation and significance of HBV precore and basal core promoter in 958 patients with chronic hepatitis B

作　　者：任晓强[1] 许智慧[1] 刘志国[2] 梁兆玲[2] 李晓东[2] 李梵[2] 毛远丽[2] 王慧芬[2] 徐东平[2] 

机构地区：[1]内蒙古农业大学生物工程学院,呼和浩特010018 [2]解放军第302医院全军传染病研究所病毒性肝炎研究室

出　　处：《解放军医学杂志》2009年第6期663-665,共3页Medical Journal of Chinese People's Liberation Army

基　　金：国家重点基础研究发展计划课题(2007CB512803);北京市自然科学基金重点课题(7091006);国家“十一五”传染病重大专项子课题(2008ZX10002-005-6,2008ZX10002-011)

摘　　要：目的检测不同病情乙型肝炎患者HBV前C/BCP区的变异特点并分析变异的意义。方法采用巢式PCR方法扩增399例轻中度慢性乙型肝炎、211例重度慢性乙型肝炎和348例慢性重型乙型肝炎患者的HBV前C/BCP区序列,PCR产物纯化后直接测序。分析10个热点变异位点及其插入/缺失变异情况,并进行统计学分析,比较这些变异对病情进展的影响。结果随着病情的加重,T1753、A1762、G1764、C1766、T1768、G1862、G1896、G1899等8个位点变异频率显著增加(P<0.01),其中5个位点的变异发生率呈现出轻中度慢性乙型肝炎<重度慢性乙型肝炎<慢性重型乙型肝炎的阶梯式上升特点。3组患者未检出突变的比率分别为27.82%、7.58%和2.01%,呈现阶梯式下降特点。此外,前C/BCP区多联变异和插入/缺失突变的发生率在病情加重时也明显增加(P<0.01),其中三联变异率依次为轻中度慢性乙型肝炎35.34%、重度慢性乙型肝炎53.56%、慢性重型乙型肝炎67.82%。结论乙型肝炎患者HBV前C/BCP区多个位点变异与慢性乙型肝炎的重症化进程相关,对乙型肝炎重症化发生机制的研究及其临床预警分析有积极意义。Objective To investigate the prevalence of HBV precore and basal core promoter （BCP） mutations in patients with hepatitis B, and to analyze its significance. Methods Sera were collected from 399 patients with chronic hepatitis B in mild or moderate degree （CHB-M）, 211 patients with chronic hepatitis B in severe degree （CHB-S）, and 348 patients with chronic severe hepatitis B （CSHB）. The precore and BCP gene fragment was amplified by nested PCR and analyzed by direct DNA sequencing. 10 most common mutation sites and their insertion/deletion were screened. The data were statistically processed to compare the influence of different variation on different disease course. Results Substitution occurrence at G1896, G1862, G1899, A1762, G1764 and T1753 significantly increased （P〈0. 01） along with aggravation of the disease The variation occurrence exhibited as a ladder-like escalation, i.e. CHB-M 〈 CHB-S 〈 CSHB, at 5 sites. The negative variation rates in these three groups were in a reverse way, i.e. CHB-M （27. 82%） 〉 CHB-S （7. 58%） 〉 CSHB （2.01 %）. In addition, multiple-site and insertion/deletion mutations obviously increased with exacerbation of the disease Three-site substitution frequency was 35. 34%, 53. 56% and 67.82% for CHB-S, CHB-S and CSHB, respectively. Conclusions There is correlation between the multiple-site mutation in HBV precore/BCP region and disease progression, and it may play an important role in understanding the pathogenesis of the CSHB and clinical prognostic analysis of the disease course.

关 键 词：肝炎病毒 乙型 前核心区 基本核心启动子 变异 

分 类 号：R512.63[医药卫生—内科学]