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华法林作为最常用的口服抗凝药物,广泛应用于慢性心房颤动、静脉血栓、肺栓塞,及心脏瓣膜置换术后等的抗凝治疗中。然而,由于华法林有效治疗剂量的范围狭窄和在个体间差异显著,加之剂量过高会导致严重出血的危险,华法林在临床上的应用受到了极大地限制。如何安全有效地应用华法林,使之达到最佳治疗效果,一直是心血管领域研究的热点和亟待解决的难题。近年来,对华法林的药物基因组学研究发现,决定华法林代谢和作用的两个主要候选基因CYP2C9和VKORC1的遗传变异型,很大程度上决定了华法林有效抗凝治疗剂量的个体间差异。本文总结了CYP2C9和VKORC1的基因变异型对华法林剂量的影响,还对近年来通过结合基因和临床因素建立的华法林剂量计算模型对预测有效华法林剂量和副作用的意义进行了综述。
Warfarin is the most commonly used oral anticoagulant and is widely used in anticoagulant therapy such as chronic atrial fibrillation, venous thrombosis, pulmonary embolism, and heart valve replacement. However, due to the narrow range of effective warfarin doses and their significant differences among individuals, and the risk of severe bleeding resulting from overdosage, the clinical use of warfarin has been severely limited. How to safely and effectively use warfarin to achieve the best therapeutic effect has always been a hot research topic in the cardiovascular field and a problem to be solved urgently. In recent years, pharmacogenomics studies of warfarin have found that the genetic variants of the two major candidate genes, CYP2C9 and VKORC1, that determine the metabolism and effects of warfarin largely determine the effective anticoagulation dose of warfarin Differences between individuals. This article summarizes the effects of gene variants of CYP2C9 and VKORC1 on the warfarin dose and also summarizes the significance of warfarin dose and side effects predicted by warfarin dose-calculation models established in recent years by combining genes and clinical factors .