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dhxpy木虫 (正式写手)
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HBV病毒YMDD变异株优势存在是病毒DNA复燃的预知因素
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Gastroenterology. 2006 Apr;130(4):1144-52. Predominance of hepatitis B virus YMDD mutants is prognostic of viral DNA breakthrough. Lee CH, Kim SO, Byun KS, Moon MS, Kim EO, Yeon JE, Yoo W, Hong SP. Department of Internal Medicine, Konkuk University Medical College, Seoul, Korea. BACKGROUND & AIMS: Hepatitis B virus (HBV) tyrosine, methionine, aspartate, aspartate (YMDD) mutants with or without additional compensatory mutations occur in chronically infected patients during lamivudine therapy and may be associated with accompanying viral breakthrough. The aim of this study was to determine whether a predominance of YMDD mutants could be a prognostic marker for occurrence of viral DNA breakthrough. METHODS: YMDD genotypes in 740 consecutive samples collected from 116 patients throughout lamivudine treatment were retrospectively analyzed using a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS)-based genotyping assay, termed restriction fragment mass polymorphism (RFMP). RFMP exploits differences in molecular masses between wild-type and variant bases of rtM204V/I following PCR amplification of HBV DNA with a lower limit of detection being 100 copies/mL. RESULTS: The study demonstrated that YMDD mutants occur throughout the course of lamivudine therapy irrespective of occurrence of viral DNA breakthrough, indicating that a mere detection of YMDD mutants could not sufficiently predict the viral DNA breakthrough, although presence of YMDD mutants is associated with high incidence of viral DNA breakthrough (odds ratio, 7.8; P = .0012; relative risk = 8.7%), and a 5-fold predominance of YMDD mutant to wild-type virus was significantly associated with viral DNA breakthrough (odds ratio, 604.5; P < .0001; relative risk = 93.8%). CONCLUSIONS: Close and periodical testing by RFMP assay should be useful to detect the predominance of YMDD mutants for monitoring drug resistance, enabling early intervention and prevention. 背景和目的：在慢性HBV感染患者进行拉米夫定治疗期间乙型肝炎病毒（HBV）发生酪氨酸、甲硫氨酸、天冬氨酸和天冬氨酸（YMDD）变异的同时合并有或无额外的代偿性突变可能伴随着病毒的复燃。 方法：在116位患者接受拉米夫定治疗期间连续接受检测的740份标本中对YMDD基因型进行了回顾性的分析，分析采用基质相关激光解吸/电离飞行时间质量频谱（MALDI-TOF MS）为基础的基因型分析法，又称为限制性片段质量多态分析（RFMP）。在野生型和发生rtM204V/I转换的变异型进行PCR扩增HBV-DNA可以发现低于100拷贝/mL限度的病毒，RFMP可以发现这一分子质量的差异。 结果：研究证实在拉米夫定治疗期间发生YMDD变异与病毒DNA复燃之间没有明显的相关性，提示单纯检测YMDD变异不能够全面的预测病毒DNA的复燃，尽管YMDD变异的存在通常伴有很高的病毒DNA复燃率（比数比，7.8；P=.0012；相对危险性=8.7%），且发生YMDD变异者发生病毒DNA复燃的可能性是野生型的5倍（比数比，604.5；P<0.0001；相对危险性=93.8%）。 结论：全程和阶段性的通过RFMP分析法可有助于检测发现发生药物抗药性的YMDD变异优势株突变，能够使我们在早期采用干预和预防措施。 |
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