华北地区HBV基因亚型特点及其与核苷(酸)类抗HBV药物耐药突变的关系  

Characteristics of HBV subgenotypes in North China and their relationship with the mutation of anti-HBV nucleoside-resistant analogs

作　　者：李晓东[1,2] 李庆虹[2] 李进[2] 周渝霞[2] 郝玉清[2] 戴久增[2] 李乐[2] 姚增涛[2] 张玲霞[2] 徐东平[2] 

机构地区：[1]军事医学科学院,北京100850 [2]解放军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》2010年第6期629-631,634,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家“十一五”传染病重大专项子课题(2008ZX10002-011);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)

摘　　要：目的研究乙型肝炎病毒(HBV)基因亚型在中国华北地区的分布情况及其对核苷(酸)类药物基因型耐药突变发生率的影响。方法提取2377例慢性乙肝(1942例)和乙肝相关肝硬化(435例)患者血清HBVDNA,采用巢式PCR扩增反转录酶(RT)基因区,对PCR产物直接测序,根据所测RT/S基因序列构建系统进化树确定HBV基因亚型,检测RT区耐药突变,将数据录入HBVdb数据库进行分析。结果感染HBV各基因亚型的例数为B1型10例(0.4%),B2型344例(14.5%),B3型6例(0.3%),B4型8例(0.3%),C1型28例(1.2%),C2型1937例(81.4%),C3型21例(0.9%),C4型6例(0.3%),D型17例(0.7%)。B2和C2亚型患者之间在性别、HBVDNA载量、总胆红素、丙氨酸氨基转移酶/天冬氨酸氨基转移酶(ALT/AST)水平、胆碱酯酶、凝血酶原活动度方面差异无统计学意义(P>0.05);慢性乙肝患者中,C2亚型病毒感染的拉米夫定耐药突变V173L、L180M、M204I和阿德福韦酯耐药突变A181V检出率显著高于B2亚型病毒感染(P<0.05);乙肝相关肝硬化患者中,B2亚型病毒感染的阿德福韦酯耐药突变N236T检出率显著高于C2亚型病毒感染(P=0.014)。结论我国华北地区流行的HBV以C型和B型为主,其中C2和B2为主要亚型,HBV基因亚型可能会影响临床核苷(酸)类药物的耐药突变发生率。Objective To analyze the geographical distribution of hepatitis B virus （HBV） subgenotypes in North China and their relationship with the mutation of anti-HBV nucleoside-resistant analogs （NA）. Methods Serum HBV DNA was extracted from 2377 patients,including 1942 with chronic hepatitis B （CHB） and 435 with hepatitis B-related liver cirrhosis （HB-LC）. A nested PCR assay was employed to amplify reverse-transcriptase （RT） domain of HBV polymerase gene. Direct PCR sequencing was performed. HBV subgenotypes were identified based on the RT/S gene sequences,and the NA-resistant mutations were detected. The data were entered into the HBVdb database for analysis. Results The cases infected with individual HBV subgenotype were 10（0.4%） for B1,344（14.5%） for B2,6（0.3%） for B3,8（0.3%） for B4,28（1.2%） for C1,1937（81.4%） for C2,21（0.9%） for C3,6（0.3%） for C4,and 17（0.7%） for D. No obvious difference was observed in sex,HBV DNA level,TBIL,ALT/AST levels,CHE and PTA between patients infected with C2 and B2 viruses （P0.05）. In CHB patients,C2 virus infection showed a higher occurrence of lamivudine-resistance mutations （V173L,L180M and M204I） and adefovir-resistance mutation A181V,than B2 virus infection （P0.05）. In HB-LC patients,a higher incidence of adefovir-resistant mutation N236T existed in B2 virus infection compared with C2 virus infection （P=0.014）. Conclusions C2 is the most predominant HBV subgenotype,followed by B2,in North China. HBV subgenotypes may have influence on NA-resistant mutation in clinic.

关 键 词：肝炎病毒 乙型 基因亚型 抗药性 病毒 突变 

分 类 号：R512.62[医药卫生—内科学]