实施基因分型指导的抗栓治疗。
Implementing genotype-guided antithrombotic therapy.
作者信息
Seip Richard L, Duconge Jorge, Ruaño Gualberto
机构信息
Genomas, Inc., 67 Jefferson Street, Hartford, CT 06106, USA.
出版信息
Future Cardiol. 2010 May;6(3):409-24. doi: 10.2217/fca.10.6.
Genotyping has the potential to improve the efficacy and safety of major antithrombotic drugs. For warfarin, the stable maintenance dose varies from 1-10 mg/day. The VKORC1 -1639G>A allele and the CYP2C9*2 and 3 alleles (cumulative frequency: 90% in Asians, 65% in Europeans and 20% in Africans), explain 45% of response variability in European and 30% in African populations. The large clinical trials COAG and EU-PACT will define the extent to which pharmacogenetic dosing affects the safety and efficacy of warfarin and coumarin derivatives. The platelet inhibitor clopidogrel requires activation by the CYP2C19 enzyme. CYP2C192 and *3 alleles (cumulative frequency: 20-50%) produce null enzyme activity, and their presence attenuates platelet inhibition and increases cardiovascular events. The US FDA-mandated drug labeling recognizes the relevance of genotyping in the selection and dosing of both warfarin and clopidogrel.
基因分型有潜力提高主要抗血栓药物的疗效和安全性。对于华法林，稳定维持剂量为每日1至10毫克。维生素K环氧化物还原酶复合体亚单位1（VKORC1）-1639G>A等位基因以及细胞色素P450 2C9（CYP2C9）2和3等位基因（累积频率：亚洲人为90%，欧洲人为65%，非洲人为20%），在欧洲人群中解释了45%的反应变异性，在非洲人群中解释了30%。大型临床试验“口服抗凝剂治疗遗传学（COAG）”和“欧洲华法林药物基因组学合作研究（EU-PACT）”将确定药物遗传学给药对华法林和香豆素衍生物安全性和疗效的影响程度。血小板抑制剂氯吡格雷需要通过细胞色素P450 2C19（CYP2C19）酶激活。CYP2C192和3等位基因（累积频率：20%-50%）产生无活性的酶，其存在会减弱血小板抑制作用并增加心血管事件。美国食品药品监督管理局（US FDA）要求的药品标签认可基因分型在华法林和氯吡格雷选择及给药方面的相关性。
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