Cytochrome P-450 Polymorphisms and Response to Clopidogrel.
Cytochrome P-450 Polymorphisms and Response to Clopidogrel.
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DOI：
10.1056/nejmoa0809171
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发表时间：
2009-01-22
影响因子：
158.5
通讯作者：
Sabatine, Marc S.
中科院分区：
文献类型：
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作者：
Mega, Jessica L.;Close, Sandra L.;Sabatine, Marc S.
背景：氯吡格雷需要通过细胞色素P-450（CYP）酶转化为活性代谢物才能发挥其抗血小板作用。编码β-内酰胺酶的基因是多态性的，与共同的等位基因赋予降低function.Methods：我们测试了β-内酰胺酶基因，活性药物代谢产物的血浆浓度，并在162名健康受试者中响应于氯吡格雷的血小板抑制的功能性遗传变异之间的关联。然后，我们在一个单独的队列中研究了这些遗传变异与心血管结局之间的关系，该队列有1477名急性冠脉综合征患者，他们在心肌梗死患者中接受了氯吡格雷治疗，以评估通过优化普拉格雷-溶栓治疗血小板抑制来改善治疗结局（TRITON-TIMI）38.结果：在接受氯吡格雷治疗的健康受试者中，至少一个CYP 2C 19功能降低等位基因的携带者与非携带者相比，携带者（约占研究人群的30%）的血浆氯吡格雷活性代谢物暴露量相对减少32.4%（P
Background: Clopidogrel requires transformation into an active metabolite by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. The genes encoding CYP enzymes are polymorphic, with common alleles conferring reduced function.Methods: We tested the association between functional genetic variants in CYP genes, plasma concentrations of active drug metabolite, and platelet inhibition in response to clopidogrel in 162 healthy subjects. We then examined the association between these genetic variants and cardiovascular outcomes in a separate cohort of 1477 subjects with acute coronary syndromes who were treated with clopidogrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38.Results: In healthy subjects who were treated with clopidogrel, carriers of at least one CYP2C19 reduced-function allele (approximately 30% of the study population) had a relative reduction of 32.4% in plasma exposure to the active metabolite of clopidogrel, as compared with noncarriers (P