CYP2C19基因多态性对氯吡格雷抗血小板治疗疗效的影响

目的：探讨CYP2C19基因分型对急性冠状动脉综合征（ACS）患者使用氯吡格雷抗血小板的疗效。方法：对某院收治的ACS患者350例，入院时即检测CYP2C19的基因多态性及血小板聚集率，给予负荷量阿司匹林300 mg、氯吡格雷300 mg。之后常规给予患者阿司匹林100 mg·d^-1、氯吡格雷75 mg·d^-1，服用1年。根据基因型将患者分为快代谢型（n=140）、中等代谢型（n=161）和慢代谢型（n=49）。治疗后第7天第2次检测血小板聚集率。采用比浊法检测5 μmol·L^-1二磷酸腺苷诱导的血小板聚集率。对所有患者进行为期1年的随访，比较不同代谢类型患者严重心脏事件和联合心脏事件的发生率。结果：快代谢性CYP2C19*1/*1共140例，占40.0%；中等代谢型CYP2C19*1/*2 146例（41.7%）、CYP2C19*1/*3 15例（4.3%）；慢代谢型CYP2C19*2/*2 35例（10.0%）、CYP2C19*2/*3 14例（4.0%）、CYP2C19*3/*3 0例。服药7 d后，3组血小板最大聚集率均明显下降（P<0.05）。中等代谢型组最大血小板聚集率较快代谢型组高，差异有显著性（P<0.05）。慢代谢型组最大血小板聚集率均较快代谢型组和中等代谢型组高，差异有显著性（P<0.05）。不同代谢类型患者严重心脏事件发生率的比较无显著差异（P>0.05），慢代谢型患者联合心脏事件的发生率高于快代谢型和中等代谢型患者（P<0.05）。结论：通过研究氯吡格雷对不同CYP2C19分型患者的抗血小板疗效，推荐对ACS患者在使用抗血小板药物时应进行基因多态性和血小板聚集率检测，及时调整抗血小板治疗方案，以预防不良心血管事件的发生。

Effect of CYP2C19 gene polymorphism on the efficacy of clopidogrel antiplatelet therapy

OBJECTIVE To investigate the Effect of CYP2C19 genotyping on antiplatelet therapy with clopidogrel in patients with acute coronary syndrome (ACS).METHODS Three hundred and fifty patients with acute coronary syndrome (ACS) in our hospital from October 2017 to January 2016 were included in this study.At admission,the gene polymorphism and platelet aggregation rate were detected,and the load dose of aspirin 300 mg and clopidogrel 300mg were given.Then the patients were routinely given aspirin 100mg and clopidogrel 75 mg.Patients were classified according to genotype as rapid metabolizer (n=140),medium metabolizer (n=161),and slow metabolizer (n=49).Platelet aggregation rate was measured a second time at 7 d after treatment.The platelet aggregation rate induced by 5 μmol·L^-1 two phosphoric acid adenosine was measured by turbidimetry.All patients were followed up for one year to compare the incidence of severe cardiac events and combined cardiac events in patients with different metabolic types.RESULTS There were 140 patients with fast metabolism CYP2C19*1/*1(40%),146 patients with medium metabolism CYP2C19*1/*2(41.7%),15 patients with CYP2C19*1/*3(4.3%),35 patients with slow metabolism CYP2C19*2/*2(10%),14 patients with CYP2C19*2/*3(4%),and 0 patients with CYP2C19*3/*3.After 7 days of medication,the maximum platelet aggregation rate decreased significantly in all three groups (P<0.05).The maximum platelet aggregation rate in the medium metabolism group was higher than that in the rapid metabolism group,and the difference was significant (P<0.05).The maximum platelet aggregation rate was significantly higher in the slow metabolizer group than in the fast metabolizer group and the medium metabolizer group.(P<0.05).There was no significant difference in the comparison of the incidence of serious cardiac events between patients with different metabolic types (P>0.05).and the incidence of combined cardiac events was higher in patients with slow metabolism than in patients with rapid and medium metabolism (P<0.05).CONCLUSION In this study,we studied the antiplatelet effect of clopidogrel on patients with different CYP2C19 subtypes.it is recommended that gene polymorphism and platelet aggregation rate should be detected in patients with ACS when using antiplatelet drugs,and the antiplatelet therapy regimen should be adjusted in time to prevent the occurrence of adverse cardiovascular events.