Inhibition of ADP-induced platelet aggregation by clopidogrel is related to CYP2C19 genetic polymorphisms
Inhibition of ADP-induced platelet aggregation by clopidogrel is related to CYP2C19 genetic polymorphisms
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DOI：
10.1111/j.1440-1681.2008.04915.x
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发表时间：
2008-08-01
影响因子：
2.9
通讯作者：
Zhou, Hong-Hao
中科院分区：
文献类型：
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作者：
Chen, Bi-Lian;Zhang, Wei;Zhou, Hong-Hao
1. 氯吡格雷是最重要的抗血栓药物之一，但在不同人群中疗效不同。本研究的目的是评估CYP2C19基因多态性在氯吡格雷抑制adp诱导的血小板聚集中的作用。18名健康男性志愿者（6名CYP2C19*1/CYP2C19*1、6名CYP2C19*1/CYP2C19*2和*3、6名CYP2C19*2/CYP2C19*2和*3）入组研究。每名受试者第一天服用氯吡格雷300 mg，然后每天服用75 mg，连续2天。在给药后4、24和72 h，分别取血测定adp诱导的血小板聚集。三种CYP2C19基因型患者在使用氯吡格雷后4、24和72 h 2和5 mmol/L adp诱导的血小板聚集量与基线相比均显著降低（P < 0.001）。CYP2C19*1/CYP2C19*1基因型患者5 mmol/L adp诱导的血小板聚集在氯吡格雷给药后4 h（分别为49.0 +/- 15.5 vs 29.7 +/- 17.4%, P = 0.029）、24 h（分别为48.7 +/- 20.5 vs 25.0 +/- 17.6%, P = 0.035）和72 h（分别为45.5 +/- 15.2 vs 26.5 +/- 15.8%, P = 0.030）高于CYP2C19*2/CYP2C19*2和CYP2C19*2和*3基因型患者。综上所述，CYP2C19*2和CYP2C19*3基因多态性降低了氯吡格雷对adp诱导的血小板聚集的抑制作用，其抑制程度取决于基因多态性的存在。
1. Clopidogrel is one of the most important antithrombotic drugs but has different efficacies in different populations. The aim of the present study was to evaluate the contribution of CYP2C19 genetic polymorphisms to the inhibition of ADP-induced platelet aggregation by clopidogrel in healthy Chinese volunteers.2. Eighteen healthy male volunteers (six CYP2C19*1/CYP2C19*1, six CYP2C19*1/CYP2C19*2and*3 and six CYP2C19*2/CYP2C19*2and*3) were enrolled in the study. Each subject took 300 mg clopidogrel on the first day and then 75 mg once daily for 2 consecutive days. Blood samples were taken to measure ADP-induced platelet aggregation at baseline and 4, 24 and 72 h after administration of the first dose of clopidogrel.3. There were significant decrease in 2 and 5 mmol/L ADP-induced platelet aggregation at 4, 24 and 72 h after clopidogrel among the three CYP2C19 genotypes compared with baseline (P < 0.001). The change in 5 mmol/L ADP-induced platelet aggregation in subjects with the CYP2C19*1/CYP2C19*1 genotype was greater than that in subjects with the CYP2C19*2/CYP2C19*2and*3 genotype at 4 h (49.0 +/- 15.5 vs 29.7 +/- 17.4%, respectively; P = 0.029), 24 h (48.7 +/- 20.5 vs 25.0 +/- 17.6%, respectively; P = 0.035) and 72 h (45.5 +/- 15.2 vs 26.5 +/- 15.8%, respectively; P = 0.030) after clopidogrel administration.4. In conclusion, CYP2C19*2 and CYP2C19*3 genetic polymorphisms reduced clopidogrel inhibition of ADP-induced platelet aggregation, with the degree of inhition dependent on the genetic polymorphism present.