乙型肝炎病毒基因型、BCP及PC区变异与拉米夫定治疗后HBV DNA反弹的关系  

Relationship of HBV genotype and bcp and pc mutations with HBV DNA rebound after lamivudine therapy

作　　者：苏明华[1] 江建宁[1] 周元平[2] 陈茂伟[1] 刘志红[1] 

机构地区：[1]广西医科大学一附院感染性疾病科,广西壮族自治区南宁市530027 [2]广州南方医院,广东省广州市510000

出　　处：《世界华人消化杂志》2007年第33期3507-3513,共7页World Chinese Journal of Digestology

基　　金：广西自然科学基金桂科资助项目;No.0342009~~

摘　　要：目的:探讨HBV基因型、C区基本核心启动子(BcP)及前C(PC)区变异与拉米夫定抗病毒治疗后HBV DNA反弹的关系.方法:应用多引物对巢式PCR法,PCR-序列分析法,检测拉米夫定治疗27例乙型肝炎患者(治疗组),以及19例从未用过抗病毒治疗患者(对照组)的HBV基因型PC区,BCP的突变位点.结果:27例HBV DNA反弹的患者9例检出G1896A变异率高于对照组(33.33% vs 5.26%,P<0.05),4例检出C1856T变异(14.81%).治疗组4份治疗前标本未检出G1896A、C1856T和BCP变异.与对照组比较,治疗组PC(G1896A)及BCP(A1762T+G1764A)双变异的患者中B基因型的构成比增高,分别为75%和50%,C基因型的构成比下降,分别为25%和50%.其中在BCP(A1762T+G1764A)变异患者中B、C基因型构成比与对照组比较有显著性差异(P<0.05).4例HBV DNA反弹患者治疗前未检出有基因变异,治疗后有2例检出变异,BCP变异1例,BCP+PC变异1例.27例HBV DNA反弹患者BCP变异4例,PC变异2例,BCP+PC变异8例.结论:BCP(T1762/A1764)变异、PC区(G1896A)变异可能与拉米夫定治疗后HBV DNA反弹有关.病毒变异导致的HBV DNA反弹可以是单基因变异引起,也可以是多个基因联合变异引起,拉米夫定治疗后B基因型患者更易发生A1762T+G1764A变异.AIM： To investigate the relationship of HBV gene mutations with HBV DNA rebound after lamivudine therapy. METHODS： Twenty-seven hepatitis B patients with HBV DNA rebound after lamivudine thera- py （therapy group） and 19 patients without antiviral therapy （control group） were investigated. HBV genotype was detected by nested PCR with multiple pair primers. Mutations of basal core promoter （BCP） and precore （PC） were identified by PCR gene sequence analysis in sera of 27 patients after HBV DNA rebound, and in sera of 4 patients before therapy in the therapy group and in sera of 19 patients in the control group.RESULTS： The ratio of BCP （A1762T ＋ G1764A） mutations in serum of patients with HBV DNA rebound was 44.44% （12/27） higher than 26.32% （5/19） in the control group, although not significantly. The mutation was not detected in the sera of 4 patients before therapy. The ratio of the PC （G1896A） mutation in serum of patients with HBV DNA rebound was 33.33% （9/27） higher than 5.26% （1/19） in the control group （P 〈 0.01）. The mutation was not detected in the sera of 4 patients before therapy. The ratio of the C1856T mutation was 14.81% （4/27） higher than 10.53%（2/19） in the control group, but not significantly. It was not detected in the sera of 4 patients before therapy. In patients with the BCP mutation （A1762T ＋ G1764A）, the constituent ratio of genotype B was 75% higher and that of genotype C was 25% lower than those in the control group （both P 〈 0.05）. In patients with mutation PC （G1896A）, the constituent ratio of genotype B was 50% higher, and that of genotype C was 50% lower than those in the control group （P 〉 0.05）. Gene mutations were not detected in four patients before lamivudine therapy but BCP and BCP ＋ PC mutations occurred in two patients after HBV rebound. In 27 patients with HBV DNA rebound, there were BCP mutations in four, PC mutation in two, and BCP ＋ PC mutation in eight. CONCLUSION： BCP （T1762/A1764�

关 键 词：乙型肝炎病毒 基因型 BCP PC区变异 拉米夫定治疗 HBV DNA反弹 

分 类 号：R512.6[医药卫生—内科学]