Objective: To investigate the impact of CYP2C19 genetic variants on antiplatelet therapy in Chinese patients with acute myocardial infarction(AMI) after primary percutaneous coronary intervention(PCI), and compare the antiplatelet effect between clopidogrel and ticagrelor with various CYP2C19 genotypes. Methods: From June 2014 to May 2015, 347 patients with AMI who underwent PCI treatment at Fuwai Hospital were enrolled in this single center prospective study, 221 cases were in clopidogrel group and 126 patients were in ticagrelor group.Two candidate single nucleotide polymorphisms (SNPs) (636 and 681 loci) of CYP2C19 gene were detected by polymerase chain reaction-restriction endonuclease method.Adenosine diphosphate (ADP)-induced platelet aggregation was measured by thromboelastography (TEG) at 24-48 hours after primary PCI. Results: There were 93 non-carriers (42.1%, 93/221), and 128 carriers (57.9%, 128/221) in clopidogrel group. There were 48 non-carriers (38.1%, 48/126), 78 carriers (61.9%, 78/126) in ticagrelor group. CYP2C19 genotype frequency was similar between two groups. TEGADP was significantly lower in clopidogrel group than in ticagrelor group (63.08±27.78 vs. 78.08±25.62, P<0.001), both for non-carriers (68.16±25.17 vs. 82.79±22.45, P=0.002) and for carriers (59.37±29.06 vs. 75.15±27.15, P<0.001). TEGADP was significantly higher in non-carriers than in carriers in clopidogrel group (P=0.02) and similar between non-carriers and carriers in ticagrelor group (P>0.05). Conclusion: The CYP2C19 gene mutation is high in the patients with AMI.The effect of antiplatelet of ticagrelor is stronger than clopidogrel, and this effect is not affected by CYP2C19 gene mutations.
目的：探讨CYP2C19等位基因突变在急性心肌梗死患者中的发生情况，比较不同等位基因携带者服用氯吡格雷或替格瑞洛产生的抗血小板作用的差别。 方法：本研究为前瞻性研究，入选2014年6月至2015年4月在阜外医院诊断为急性心肌梗死行急诊经皮冠状动脉介入治疗(PCI)的患者，氯吡格雷组221例，替格瑞洛组126例。应用聚合酶链反应-限制性核酸内切法检测CYP2C19基因636及681位点的基因型，采用血栓弹力图(TEG)检测患者PCI术后24～48 h的血小板功能，并以血栓弹力图测定ADP诱导的血小板抑制率(TEGADP)反映血小板功能。 结果：氯吡格雷组CYP2C19基因快代谢型为42.1%(93/221)，功能缺失等位基因携带者为57.9%(128/221)；替格瑞洛组快代谢型为38.1%(48/126)，功能缺失等位基因携带者为61.9%(78/126)。两组CYP2C19基因各基因型携带频率差异无统计学意义。氯吡格雷组总TEGADP(63.08±27.78比78.08±25.62，P<0.001)、CYP2C19基因快代谢型TEGADP(68.16±25.17比82.79±22.45，P＝0.002)、功能缺失等位基因携带者TEGADP(59.38±29.06比75.15±27.15，P<0.001)均低于替格瑞洛组。氯吡格雷组快代谢型TEGADP明显高于其功能缺失等位基因携带者(P＝0.02)。替格瑞洛组的快代谢型TEGADP与其功能缺失等位基因携带者比较，差异无统计学意义(P＝0.125)。 结论： CYP2C19基因突变在本组急性心肌梗死行急诊PCI的患者中发生率高达50%以上。CYP2C19基因突变的患者，氯吡格雷的抗血小板作用降低。替格瑞洛的抗血小板作用强于氯吡格雷，且这一作用不受CYP2C19基因突变的影响。.
Keywords: Antiplatelet agents; Drug-eluting stents; Myocardial infarction; Polymorphism, single nucleotide.