Warfarin pharmacogenetics.

Warfarin pharmacogenetics.
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DOI:
10.1016/j.tcm.2014.09.001
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发表时间:
2015-01
影响因子:
9.3
通讯作者:
Cavallari, Larisa H.
Cavallari, Larisa H.
中科院分区:
医学2区
文献类型:
--
作者:
Johnson, Julie A.;Cavallari, Larisa H.

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细胞色素P450(P450)2C 9和维生素K环氧化物还原酶复合物1(VKORC 1)基因型与华法林剂量要求强烈且一致相关,并且结合遗传和临床信息的给药算法已被证明可预测稳定的华法林剂量。然而,评估基因型指导华法林剂量的临床试验产生了混合结果,对这种方法的实用性提出了质疑。最近的试验使用替代标志物作为终点,而不是临床终点,进一步复杂化的数据转化为临床实践。目前的数据不支持基因检测来指导华法林剂量,但在基因型数据可用的情况下,在欧洲血统的人群中使用这些数据是合理的。预期结果数据来自正在进行的试验,观察性研究仍在继续,需要更多的工作来定义在少数人群中纳入适当变体的给药算法;所有这些将进一步形成关于基因型指导的华法林给药临床效用的指南和建议。
The cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase complex 1 (VKORC1) genotypes have been strongly and consistently associated with warfarin dose requirements, and dosing algorithms incorporating genetic and clinical information have been shown to be predictive of stable warfarin dose. However, clinical trials evaluating genotype-guided warfarin dosing produced mixed results, calling into question the utility of this approach. Recent trials used surrogate markers as endpoints rather than clinical endpoints, further complicating translation of the data to clinical practice. The present data do not support genetic testing to guide warfarin dosing, but in the setting where genotype data are available, use of such data in those of European ancestry is reasonable. Outcomes data are expected from an on-going trial, observational studies continue, and more work is needed to define dosing algorithms that incorporate appropriate variants in minority populations; all these will further shape guidelines and recommendations on the clinical utility of genotype-guided warfarin dosing.
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