Lev Eli I, Patel Rajnikant T, Guthikonda Sasidhar, Lopez David, Bray Paul F, Kleiman Neal S
The Methodist DeBakey Heart Center, The Methodist Hospital and Baylor College of Medicine, Section of Cardiology, 6565 Fannin St./Mail Station F-1090, Houston, TX 77030, USA.
Thromb Res. 2007;119(3):355-60. doi: 10.1016/j.thromres.2006.02.006. Epub 2006 Mar 6.
There is wide variability in the responses of individual patients to aspirin and clopidogrel. Polymorphisms of several platelet receptors have been related to increased platelet aggregation. We therefore aimed to evaluate whether these polymorphisms are related to altered response to aspirin or clopidogrel.
Patients (n=120) undergoing percutaneous coronary intervention who received aspirin for > or =1 week but not clopidogrel were included. Blood samples were drawn at baseline and 20-24h after a 300-mg clopidogrel dose. Aspirin insensitivity was defined as 5 microM ADP-induced aggregation > or =70% and 0.5 mg/mL arachidonic acid-induced aggregation > or =20%. Clopidogrel insensitivity was defined as baseline minus post-treatment aggregation < or =10% in response to 5 and 20 microM ADP. PlA polymorphism of glycoprotein IIIa, T744C polymorphism of the P2Y(12) gene and the 1622A>G polymorphism of the P2Y(1) gene were genotyped by polymerase chain reaction.
There were no differences in polymorphism frequencies between drug-insensitive vs. drug-sensitive patients. There were also no significant differences in response to aspirin (assessed by arachidonic acid-induced aggregation) or to clopidogrel (assessed by ADP-induced aggregation or activation markers) when patients were grouped according to genotype. The only trend observed was lower reduction in PAC-1 binding following clopidogrel in PlA(2) carriers (P=0.065).
We did not find an association between polymorphisms in the platelet receptors GP IIIa, P2Y(12) or P2Y(1) and response to aspirin or clopidogrel in cardiac patients. These findings suggest that the variability in response to anti-platelet drugs is multi-factorial and is not caused only by single gene mutations.
个体患者对阿司匹林和氯吡格雷的反应存在很大差异。几种血小板受体的多态性与血小板聚集增加有关。因此，我们旨在评估这些多态性是否与对阿司匹林或氯吡格雷的反应改变有关。
纳入接受经皮冠状动脉介入治疗且服用阿司匹林≥1周但未服用氯吡格雷的患者（n = 120）。在基线时以及给予300 mg氯吡格雷剂量后20 - 24小时采集血样。阿司匹林不敏感定义为5 μM ADP诱导的聚集≥70%且0.5 mg/mL花生四烯酸诱导的聚集≥20%。氯吡格雷不敏感定义为对5和20 μM ADP反应时，基线减去治疗后聚集≤10%。通过聚合酶链反应对糖蛋白IIIa的PlA多态性、P2Y(12)基因的T744C多态性和P2Y(1)基因的1622A>G多态性进行基因分型。
药物不敏感患者与药物敏感患者之间的多态性频率没有差异。当根据基因型对患者进行分组时，对阿司匹林（通过花生四烯酸诱导的聚集评估）或氯吡格雷（通过ADP诱导的聚集或激活标志物评估）的反应也没有显著差异。观察到的唯一趋势是PlA(2)携带者在服用氯吡格雷后PAC - 1结合的降低幅度较小（P = 0.065）。
我们未发现血小板受体GP IIIa、P2Y(12)或P2Y(1)的多态性与心脏病患者对阿司匹林或氯吡格雷的反应之间存在关联。这些发现表明，抗血小板药物反应的变异性是多因素的，并非仅由单基因突变引起。
