DO VKORC1 AND CYP2C9 MUTATIONS LEAD TO WARFARIN RESISTANCE?

K. Yay, Alper İbrahim TOSYA, Zafer Cengiz ER
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Abstract

The objective of this study was to determine the influence of VKORC1 and CYP2C9 polymorphisms on warfarin resistant patients. Warfarin resistance is described as the inability to prolong the prothrombin time or raise the INR up to the 2 therapeutic range when the drug is given at typically doses. Polymorphisms may play a role as some VKORC1 and CYP2C9 variant alleles are known to be associated with these circumstances. 28 patients who were taking warfarin more than 15 mg/day and had INR values below 2.1 and had thromboembolic events while using warfarin were enrolled in this study. Heterozygote mutation in the VKORC1 gene was identified in 15 of 28 patients. Seven patients had heterozygote mutation of the CYP2C9 gene, and that may correspond to the ultrarapid metabolism of warfarin. VKORC1 and CYP2C9 polymorphism contribute to the difference in dose requirement amongst the patients, but other additional possible factors may play a role in different races. We suggest that medicians may use this tests before starting warfarin therapy and shape the treatment course according to this results.
vkorc1和cyp2c9突变会导致华法林耐药吗?
本研究的目的是确定VKORC1和CYP2C9多态性对华法林耐药患者的影响。华法林耐药被描述为不能延长凝血酶原时间或将INR提高到2治疗范围,当药物以典型剂量给予时。多态性可能起作用,因为已知一些VKORC1和CYP2C9变异等位基因与这些情况有关。28例服用华法林超过15mg /天且INR值低于2.1且在使用华法林期间发生血栓栓塞事件的患者纳入本研究。28例患者中有15例发现VKORC1基因杂合子突变。7例患者CYP2C9基因杂合子突变,可能与华法林的超快速代谢相对应。VKORC1和CYP2C9多态性导致了患者剂量需求的差异,但其他可能的因素可能在不同种族中起作用。我们建议医生在开始华法林治疗前使用此测试,并根据此结果制定治疗过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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