乙型肝炎病毒基因型及亚型与YMDD、前C和C基因启动子变异的关系  

Relationship between hepatitis B virus genotypes/subgenotypes and development of YMDD and pre-core/core promoter mutations in Chinese patients with chronic hepatitis B

作　　者：王雪刚[1] 王战会[1] 马世武[1] 梁敏锋[1] 周彬[1] 侯金林[1] 

机构地区：[1]广州南方医科大学南方医院感染内科,510515

出　　处：《肝脏》2007年第2期95-98,共4页Chinese Hepatology

基　　金：国家自然科学基金(30500434)

摘　　要：目的探讨乙型肝炎病毒(HBV)基因型及亚型与YMDD变异的关系,以及前C基因区终止密码变异(A1896)、基本核心启动子(BCP)区T1762/A1764变异在Ba、C1和C2三种基因亚型中的发生情况。方法采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)法对211例服用拉米夫定后发生YMDD耐药变异的患者HBV进行基因型、基因亚型、A1896及T1762/A1764变异检测。结果211份标本中B基因型占50.7%(107/211),C基因型占49.3%(104/211),与广东地区对照人群HBV基因型分布情况相比无统计学差异(χ2=0.508,P=0.476)。进一步亚型分析发现,107份B基因型全部为Ba亚型;C基因型有C1和C2两种亚型,其中C1亚型占64.4%(67/104),C2亚型占35.6%(37/104),与广东地区对照人群C基因亚型分布情况相比也无统计学差异(χ2=0.043,P=0.836)。A1896变异在Ba亚型中的分布最高(41/107,38.3%),C2亚型次之(13/39,33.3%),C1亚型最低(9/65,13.8%),变异在不同基因亚型中的分布有统计学差异(χ2=11.839,P=0.03)。T1762/A1764变异在C1亚型中的分布最高(34/65,52.3%),C2亚型次之(17/39,43.6%),Ba亚型最低(23/107,21.5%),T1762/A1764变异在不同基因亚型中的分布有统计学差异(χ2=18.384,P<0.001)。结论HBV基因型及亚型并不影响YMDD变异的发生,但3种基因亚型发生A1896及T1762/A1764变异的模式存在明显不同。Objective To investigate the relationship between hepatitis B virus （HBV） genotypes/subgenotypes and the development of YMDD mutation, as well as pre-core stop code （A1896） and basic core promoter （BCP/ T1762/A1764） mutations in Chinese patients with chronic hepatitis B. Methods HBV genotypes, subgenotypes, A1896 and T1762/A1764 mutations were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） in 211 chronic HBV carriers with YMDD mutant strain after receiving the treatment of lamivudine. Results In 211 patients, 107 genotype B （50.7%）, 104 genotype C （49.3%） were identified, respectively. No statistical difference was found when compared with the distribution of HBV genotypes in Guangdong province （χ^2 = 0. 508; P = 0. 476）. Further analysis showed all genotype B belong to subgenotype Ba, 67 with C1 subgenotype （67/104, 64.4% ） and 37 with C2 subgenotype （37/104, 35.6% ）. No significant difference was found compared with the distribution of C1/C2 in Guangdong （χ^2 = 0.043; P = 0.836）. Prevalence of A1896 was significantly higher in patients with Ba （41/107, 68.3%） than C2 （13/19, 33.3%） and C1 subgenotype （9/65, 13.8%） （χ^2 = 11.839, P =0.03）. Development of T1762/A1764 mutations was significantly higher in C1 （34/65,52.3 % ） than C2 （ 17/39, 43.6% ） and Ba subgenotype （23/107, 21.5 % ） （χ^2 = 18.384;P 〈 0.00l）. Conclusion There was no significant difference in development of YMDD mutation in different genotypes and subgenotypes of HBV in Guangdong provine. But the prevalence of A1896 and T1 762/A1 764 mutations was significantly different in genotypes and subgenotypes of HBV in Chinese patients with chronic hepatitis B.

关 键 词：乙型肝炎病毒 基因型 亚型 变异 

分 类 号：R512.62[医药卫生—内科学]