Warfarin pharmacogenetics.
Warfarin pharmacogenetics.
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DOI：
10.1592/phco.28.9.1084
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发表时间：
2008-09
期刊：
影响因子：
4.1
通讯作者：
Veenstra DL
中科院分区：
文献类型：
--
作者：
Limdi NA;Veenstra DL
最近的药品说明书更新突出了华法林在改善华法林安全性和有效性方面的潜在作用，因此对华法林治疗的药物遗传学产生了重大兴趣。在此，我们审查的两个关键基因的影响，CYP 2C 9和VKORC 1，华法林反应的证据，并讨论目前的知识对临床实践的影响。CYP 2C 9和VKORC 1基因型对华法林剂量需求的影响已在观察性研究和随机临床试验中在不同种族/民族患者组中得到一致证实。已经开发了结合临床、人口统计学和遗传信息的给药算法，以帮助选择起始华法林剂量。此外，CYP 2C 9变异基因型与严重出血事件风险显著增加相关。然而，迄今为止，前瞻性对照研究的证据尚未证明结合基因型指导治疗在改善抗凝控制、预防或降低出血或血栓栓塞并发症风险方面的额外获益。旨在评估基因型指导治疗在改善预后方面的有效性的研究工作正在进行中。然而，目前可用的证据不支持在开始华法林治疗的一般患者人群中常规使用CYP 2C 9和VKORC 1基因分型。
There has been significant interest in the pharmacogenetics of warfarin therapy with the recent package insert update highlighting its potential role in improving the safety and effectiveness of warfarin. Herein we review the evidence of the influence of the two key genes of interest, CYP2C9 and VKORC1, on warfarin response, and discuss the implications of current knowledge for clinical practice. The influence of CYP2C9 and VKORC1 genotype on warfarin dose requirements has been consistently demonstrated in diverse racial/ ethnic patient groups in observational studies and randomized clinical trails. Dosing algorithms have been developed that incorporate clinical, demographic, and genetic information to help select a starting warfarin dose. Furthermore, CYP2C9 variant genotypes have been associated with a significantly increased risk of serious bleeding events. However evidence to date from prospective, controlled studies has not demonstrated an added benefit of incorporating genotype-guided therapy in improving anticoagulation control, preventing or reducing the risk of hemorrhagic or thromboembolic complications. Research efforts designed to evaluate the effectiveness of genotype-guided therapy in improving outcomes are underway. However the routine use of CYP2C9 and VKORC1 genotyping in the general patient population initiating warfarin therapy is not supported by evidence currently available.
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影响因子：
3.6
作者：
Dickmann, LJ;Rettie, AE;Schwarz, UI
通讯作者：
Schwarz, UI
影响因子：
6.7
作者：
Geisen, C;Watzka, M;Oldenburg, J
通讯作者：
Oldenburg, J
DOI：
10.1097/01.fpc.0000114760.08559.dc
发表时间：
2004-08-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Hillman, MA;Wilke, RA;Burmester, JK
通讯作者：
Burmester, JK
影响因子：
--
作者：
Chiquette, E;Amato, MG;Bussey, HI
通讯作者：
Bussey, HI
影响因子：
20.3
作者：
D'Andrea, G;D'Ambrosio, RL;Margaglione, M
通讯作者：
Margaglione, M