Effects of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and clinical outcome in patients with acute coronary syndromes undergoing stent-based coronary intervention  

作　　者：TANG Xiao-fang ZHANG Jia-hui WANG Jing HAN Ya-ling XU Bo QIAO Shu-bin WU Yong-jian CHEN Jue WU Yuan CHEN Ji-lin GAO Run-lin YANG Yue-jin YUAN Jin-qing 

机构地区：[1]Department of Cardiology, Fu Wai Hospital and Cardiovascular Institute, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China [2]Department of Cardiology, Institute of Cardiovascular Research of People's Liberation Army, Shenyang Northern Hospital, Shenyang, Liaoning 110840, China

出　　处：《Chinese Medical Journal》2013年第6期1069-1075,共7页中华医学杂志（英文版）

摘　　要：Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 （group 1）, 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 （group 2）, 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 （group 3）, and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 （group 4）. Group 4 had the lowest ADP-inhibition （49.74＋32.61） and the highest prevalence of clopidogrel low response （29.7%） of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 （8.5%） than in the other three groups; the rate of composite primary endpoints in group 2 （2.9%） and group 3 （3.7%） were not significantly different than that of group 1 （1.5%）. Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 （group 1）, 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 （group 2）, 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 （group 3）, and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 （group 4）. Group 4 had the lowest ADP-inhibition （49.74＋32.61） and the highest prevalence of clopidogrel low response （29.7%） of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 （8.5%） than in the other three groups; the rate of composite primary endpoints in group 2 （2.9%） and group 3 （3.7%） were not significantly different than that of group 1 （1.5%）. Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.

关 键 词：CLOPIDOGREL acute coronary syndromes CYP2 C19 P2 Y12 platelet reactivity 

分 类 号：R541.4[医药卫生—心血管疾病]