HBV基本C区启动子区位点突变及病毒载量与拉米夫定耐药的关系

The relationship between basal core promoter mutations in the hepatitis B virus genome or serum viral load and HBV lamivudine resistance

目的探讨乙型肝炎病毒（HBV）基本C区启动子（BCP）区第1762、1764位点突变及病毒载量与拉米夫定治疗慢性乙型肝炎（CHB）P区第552、528位点变异产生的关系。方法选择CHB且未接受过拉米夫定治疗的患者56例，应用拉米夫定治疗6个月，采用乙型肝炎病毒基因多态性检测芯片对拉米夫定治疗前后乙型肝炎病毒BCP区第1762、1764位点，P区第552、528位点进行检测，同时对患者治疗前后血清病毒载量进行检测。对比分析BCP区第1762、1764位点突变患者（A组）和未突变患者（B组）应用拉米夫定治疗6个月后，P区第552、528位点变异率，以及治疗前后血清病毒载量水平。结果（1）应用拉米夫定治疗6个月后，A组P区第552、528位点总突变率显著高于B组（P〈O．05）；第552、528单位点以及第552和528双位点突变率两组相比较差异均无统计学意义（P〉O．05）。（2）A组患者治疗前血清病毒载量水平显著高于B组患者（P〈O．05）。（3）产生P区第552、528位点变异患者治疗前血清病毒载量水平，显著高于P区未变异患者（P〈O．05）。结论（1）乙型肝炎病毒BCP区第1762、1764位点突变可增加拉米夫定治疗的耐药率。（2）BCP区第1762、1764位点突变可增加乙型肝炎病毒的复制水平。（3）BCP区位点突变所引起的乙型肝炎病毒大量复制可能是导致拉米夫定耐药率增加的主要原因。

Objective To elucidate the relationship between mutations in the basic core promoter （BCP） region at nucleotide 1762/1764 in the hepatitis B virus （HBV） genome or serum viral load and HBV lamivudine resistance. Methods Fifty-six patients with chronic hepatitis B （CHB） were ana- lyzed before lamivudine therapy. Mutations in the BCP region at nucleotide 1762/1764 and in the P re- gion at nucleotide 552/528 were detected by hepatitis B gene polymorphism chip after 6 months＇ treat- ment of lamivudine. Meanwhile, serum viral load were determined by real time fluorimetry PCR at the zero and 6th month after treatment with lamivudine. The rate of mutations in the P region at nucleo- tide 552/528 from patients with and without mutations in the BCP region were analyzed comparatively after the patients were treated with lamivudine/or 6 months. Serum viral load from patients were ana- lyzed before and after lamivudine therapy. Results （1）The rate of mutation in the P region at nucleo- tide 552 or 528 in HBV BCP gene mutation group were significantly higher than that of no BCP muta- tion group （P〈0.05）. There was no significantly difference of mutation rate of the P region at nucle- otide 552 or 528, nuclectide 552 and 528 between with and without BCP gene mutation （P〉0.05）. （2） Serum viral load from BCP mutation group was significantly higher than that of no BCP mutation group （P〈0.01）. （3） Serum viral load from patients with 552/528 mutations was significantly higher than that of patients without 552/528 mutations before lamivudine therapy. Conclusion （1） The mu- tation in HBV BCP region at nucleotide 1762/1764 may increase the lamivudine-resistant rate. （2） The mutation in HBV BCP region at nucleotide 1762/1764 may contribute to high level of serum viral load. （3） The high level of serum HBV DNA caused by mutation in HBV BCP region is main reason for HBV lamivudine resistance.