乙型肝炎病毒(HBV)基因型与YMDD变异、YMDD变异类型的关系研究

A Study on the relationship between HBV genotypes,YMDD mutation,and YMDD mutational patterns in patients with chronic hepatitis B(CHB) during lamivudine treatment

目的:探讨乙型肝炎病毒(HBV)基因型与拉米夫定耐药的变异、变异类型等的关系。方法:选取158例慢性乙型肝炎患者作为研究对象,在接受拉米夫定治疗前后,分别检测和分析慢性乙型肝炎患者HBV的基因型、病毒水平以及HBV YMDD变异;并将测序结果与GenBank中标准基因型序列进行比较分析。结果:在158例接受拉米夫定治疗的慢性乙型肝炎患者中,B基因型为85例(53.80%),C基因型为73例(46.20%);其中,C基因型的YMDD突变率与B基因型的YMDD突变率相比有显著性差异(43.84%vs 7.06%,P<0.01);并且,C基因型的YIDD突变率明显高于B基因型(81.25%vs 33.33%,P<0.01),而B基因型的YVDD突变率明显高于C基因型(66.67%vs 18.75%,P<0.01)。结论:在拉米夫定治疗过程中,HBV C基因型较易出现YMDD变异;并且B基因型以YVDD变异类型为主,C基因型以YIDD变异类型为主,这可能对拉米夫定的临床用药具有指导意义。

[Objective]This study aims to investigate the relationship between HBV genotypes,YMDD mutation,and YMDD mutational patterns in patients with chronic hepatitis B(CHB) during lamivudine treatment.[Method]One hundred and fifty-eight chronic hepatitis B patients treated with lamivudine for more than one year were employed in the study.HBV genotype was detected by the ELISA,HBV DNA was measured by fluorescence quantitative FCR,and YMDD mutations were analyzed by DNA sequencer.[Result]HBV genotype B and C accounted for 53.80%and 46.20%,respectively.Significant difference was found between patients of YMDD mutants with genotype B and C(43.84%vs 7.06%,P< 0.01).The occurrence of YIDD mutant was lower in genotype B than that in genotype C((33.33%vs 81.25%,P < 0.01),whereas YVDD mutant in genotype B(66.67%) was higher than that in genotype C(18.75%,P < 0.01).[Conclusion]There was significant difference in development of YMDD mutation in different genotypes,and YMDD mutational patterns were different between genotypes B and C,which is valuable for lamivudine treatment against HBV in clinic.