Liang Wei-feng, Yang Dan-hong, Shen Yue-hong, Xie Yuan-jun, Zhao Nian-feng
Department of Infectious Diseases, First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310003, China.
Zhonghua Gan Zang Bing Za Zhi. 2003 May;11(5):302-4.
To study the types and emergence time of YMDD motif mutation in hepatitis B virus (HBV) polymerase gene during lamivudine treatment.
The serum samples were collected from 33 patients with HBV DNA rebounding and 2 non-responders after at least one year lamivudine treatment. HBV polymerase gene was amplificated by PCR, then the products were detected by restriction fragment length polymorphism (RFLP) and by direct sequence analysis.
The variants with YMDD mutation were 14 out of the 35 patients. Mutation patterns detected in these patients included four YIDD, six YVDD, three YI/VDD and one YI/MDD. The mean emergence time of YMDD variants was 11.07+/-3.65 months after the treatment, and the earliest one and the latest one occurred 5 months and 17 months after the treatment respectively. The emergence times of YIDD, YVDD, YI/VDD were (10.00 +/- 1.41) months, (11.67 +/- 4.41) months and (13.33 +/- 3.31) months respectively, which had no statistical significance (F = 0.543, P < 0.05). Three patients treated with lamivudine 200 mg every day after the mutation were followed up for 6 months, whose HBV variants had not vanished.
There are many kinds of HBV variants after lamivudine treatment, including YIDD, YVDD, YI/VDD and YI/MDD. The emergence time of variants is quite variable between different types and the mean time is (11.07 +/- 3.65) months after treatment, and there is no relationship between the type of YMDD mutation and the time of lamivudine administration.
研究拉米夫定治疗期间乙型肝炎病毒(HBV)聚合酶基因YMDD基序突变的类型及出现时间。
收集33例拉米夫定治疗至少1年后HBV DNA反弹患者及2例无反应者的血清样本。采用聚合酶链反应(PCR)扩增HBV聚合酶基因,产物经限制性片段长度多态性(RFLP)及直接序列分析检测。
35例患者中14例出现YMDD突变。这些患者检测到的突变模式包括4例YIDD、6例YVDD、3例YI/VDD和1例YI/MDD。YMDD变异体的平均出现时间为治疗后11.07±3.65个月,最早的在治疗后5个月出现,最晚的在治疗后17个月出现。YIDD、YVDD、YI/VDD的出现时间分别为(10.00±1.41)个月、(11.67±4.41)个月和(13.33±3.31)个月,差异无统计学意义(F = 0.543,P < 0.05)。3例突变后每日服用200 mg拉米夫定的患者随访6个月,其HBV变异体未消失。
拉米夫定治疗后有多种HBV变异体,包括YIDD、YVDD、YI/VDD和YI/MDD。不同类型变异体的出现时间差异较大,平均为治疗后(11.07±3.65)个月,YMDD突变类型与拉米夫定用药时间无关。