血栓弹力图法和VerifyNow P2Y12法评估CYP2C19基因多态性对氯吡格雷反应性的影响

The effect of CYP2C19 gene polymorphisms on clopidogrel responsiveness in patients with acute coronary syndrome evaluated by thromboelastogram and VerifyNow P2Y12 assay

目的:通过血栓弹力图法(TEG)和VerifyNow P2Y12法检测来评估CYP2C19基因多态性对急性冠脉综合征(ACS)患者服用氯吡格雷疗效的影响,并比较2种方法检测结果的差异。方法:入选2017年10月至2018年10月因ACS入院且服用氯吡格雷(75 mg·d^-1)和阿司匹林(100 mg·d^-1)的患者230例,使用焦磷酸测序检测其CYP2C19基因型,并在服用氯吡格雷7 d后,使用TEG法检测其二磷酸腺苷(ADP)诱导的血小板聚集抑制率和VerifyNow P2Y12法检测其血小板反应单位(PRU)。结果:TEG法结果显示CYP2C19快代谢型、中间代谢型和慢代谢型患者出现氯吡格雷抵抗的比例分别为8.9%、40.2%和59.4%。VerifyNow P2Y12法检测结果显示各代谢型患者出现氯吡格雷抵抗的比例分别为6.9%、29.9%和50.0%。慢代谢型及中间代谢型患者出现氯吡格雷抵抗的概率明显高于快代谢组(P<0.05)。2种方法氯吡格雷抵抗检出率差异无显著性(P>0.05),检测结果显著相关(r=-0.719,P<0.001)。结论:CYP2C19基因多态性显著影响ACS患者服用氯吡格雷的疗效。TEG法和VerifyNow P2Y12法检测抗血小板聚集结果具有相关性。

OBJECTIVE To evaluate the effect of CYP2C19 gene polymorphisms on the efficacy of clopidogrel in patients with acute coronary syndrome(ACS) using thromboelastogram(TEG) and VerifyNow P2Y12 assay, and to compare the results of the two methods. METHODS A total of 230 patients who were admitted with ACS and took clopidogrel(75 mg·d^-1) and aspirin(100 mg·d^-1) from October 2017 to October 2018 were enrolled. The CYP2C19 genotype was detected by pyrosequencing. After taking aspirin 100 mg·d^-1 and clopidogrel 75 mg·d^-1 for 7 days, TEG and VerifyNow P2Y12 assay were applied to detect the ADP-induced platelet inhibition rate and platelet response unit, respectively. RESULTS The results of TEG showed that the proportions of clopidogrel resistance in poor metabolizers(PM), intermediate metabolizers(IM), and extensive metabolizers(EM) were 8.9%, 40.2%, and 59.4%, respectively. The results of VerifyNow P2Y12 assay showed that the proportions of clopidogrel resistance in PM, IM, and EM were 6.9%, 29.9%, and 50.0%, respectively. The proportions of clopidogrel resistance in PM and IM groups were significantly higher than those of EM group(P<0.05). No significant difference in the positive rate of clopidogrel resistance between TEG and VerifyNow P2 Y12 assay was observed. The ADP-induced platelet inhibition rate was negatively correlated with PRU(r=-0.719, P<0.001). CONCLUSION CYP2C19 gene polymorphisms have significant effects on the efficacy of clopidogrel in patients with ACS. High correlation between the antiplatelet aggregation results detected by TEG and VerifyNow P2Y12 assay was observed.