Pharmacogenetic studies with oral anticoagulants. Genome-wide association studies in vitamin K antagonist and direct oral anticoagulants.
Pharmacogenetic studies with oral anticoagulants. Genome-wide association studies in vitamin K antagonist and direct oral anticoagulants.
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DOI：
10.18632/oncotarget.25579
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发表时间：
2018-06-26
期刊：
影响因子：
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通讯作者：
Fernandez-Cadenas I
中科院分区：
文献类型：
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作者：
Cullell N;Carrera C;Muiño E;Torres N;Krupinski J;Fernandez-Cadenas I
口服抗凝剂（OA）是预防房颤（AF）和心源性卒中患者心血管事件和复发的推荐药物。我们进行了文献检索，以审查OAs药物基因组学的现状，重点是在接受维生素K拮抗剂（VKA）和直接口服抗凝剂（DOAC）治疗的患者中进行的全基因组关联研究（GWA）。VKA：长期以来一直使用warcantine，acenocoumarol，fluindione和phenprocoumon，但它们的个体间变异性和狭窄的治疗/安全比使它们的剂量变得困难。GWA在发现与VKA反应相关的遗传变异方面很有用。VKA药物遗传学中涉及的主要基因为：VKORC 1、CYP 2C 19和CYP 4F 2。这些基因的变异体已被纳入药物遗传学算法中，以根据其基因型和临床变量预测每例患者的VKA剂量。DOAC：达比加群、阿哌沙班、利伐沙班和依度沙班已被批准用于AF患者。它们具有稳定的药代动力学，无需常规血液检查，从而避免了VKA的大部分缺点。除了在接受达比加群治疗的患者中进行的GWA外，没有DOAC的全基因组药物基因组学数据。药物基因组学可用于预测更好的临床反应，避免抗凝治疗患者的不良事件，为每位患者确定最合适的抗凝药物。目前的药物基因组学数据显示，影响VKA或DOAC的多态性是不同的，因此可以得出结论，基于药物基因组学的个性化药物是可能的。然而，需要更多的研究，以实现个性化医疗在临床实践中与OA和基础上的药物遗传学的DOAC。
Oral anticoagulants (OAs) are the recommended drugs to prevent cardiovascular events and recurrence in patients with atrial fibrillation (AF) and cardioembolic stroke. We conducted a literature search to review the current state of OAs pharmacogenomics, focusing on Genome Wide Association Studies (GWAs) in patients treated with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). VKAs: Warfarin, acenocoumarol, fluindione and phenprocoumon have long been used, but their interindividual variability and narrow therapeutic/safety ratio makes their dosage difficult. GWAs have been useful in finding genetic variants associated with VKAs response. The main genes involved in VKAs pharmacogenetics are: VKORC1, CYP2C19 and CYP4F2. Variants in these genes have been included in pharmacogenetic algorithms to predict the VKAs dose individually in each patient depending on their genotype and clinical variables. DOACs: Dabigatran, apixaban, rivaroxaban and edoxaban have been approved for patients with AF. They have stable pharmacokinetics and do not require routine blood checks, thus avoiding most of the drawbacks of VKAs. Except for a GWAs performed in patients treated with dabigatran, there is no Genome Wide pharmacogenomics data for DOACs. Pharmacogenomics could be useful to predict the better clinical response and avoid adverse events in patients treated with anticoagulants, identifying the most appropriate anticoagulant drug for each patient. Current pharmacogenomics data show that the polymorphisms affecting VKAs or DOACs are different, concluding that personalized medicine based on pharmacogenomics could be possible. However, more studies are required to implement personalized medicine in clinical practice with OA and based on pharmacogenetics of DOACs.