CYP2C19＊2 and Other Allelic Variants Affecting Platelet Response to Clopidogrel Tested by Thrombelastography in Patients with Acute Coronary Syndrome  

作　　者：Jian Liu Xiao-Yan Nie Yong Zhang Yun Lu Lu-Wen Shi Wei-Min Wang 

机构地区：[1]Department of Cardiology, Peking University People's Hospital, Beijing 100044, China [2]School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China [3]Department of Pharmacy, Hennepin County Medical Center, Minneapolis, Minnesota 55415, USA

出　　处：《Chinese Medical Journal》2015年第16期2183-2188,共6页中华医学杂志（英文版）

摘　　要：Background：To investigate the contributions ofCYP2C 19 polymorphisms to the various clopidogrel responses tested by thrombelastography （TEG） in Chinese patients with the acute coronary syndrome （ACS）.Methods：Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy.CYP2C 19 loss of function （LOF） and gain of function （GOF） genotype,adenosine 5＇-diphosphate （ADP）-channel platelet inhibition rate （PIR） tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients.Results：High on-treatment platelet reactivity （HTPR） prevalence defined by PIR 〈30% by TEG in ADP-channel was 32.76% （38/116）.With respect to the normal wild type,CYP2C 19＊2,and ＊3 LOF alleles,and ＊ 17 GOF alleles,patients were classified into three metabolism phenotypes：41.38% were extensive metabolizers （EMs）,56.90% were intermediate metabolizers （IMs）,and 1.72% were poor metabolizers （PMs）.Of the enrolled patients,31.47%,5.17%,and 0.43%,respectively,were carriers of ＊2,＊3,and ＊ 17 alleles.The HTPR incidence differed significantly according to CYP2C 19 genotypes,accounting for 18.75%,41.54%,and 100.00% in EMs,IMs,and PMs,respectively.Eighteen （17.24%） ischemic events occurred during the 3-month follow-up,and there was a significant difference in ischemic events between HTPR group and nonhigh on-treatment platelet reactivity group.Conclusions：Genetic CYP2C 19 polymorphisms are relative to the inferior,the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS.Background：To investigate the contributions ofCYP2C 19 polymorphisms to the various clopidogrel responses tested by thrombelastography （TEG） in Chinese patients with the acute coronary syndrome （ACS）.Methods：Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy.CYP2C 19 loss of function （LOF） and gain of function （GOF） genotype,adenosine 5＇-diphosphate （ADP）-channel platelet inhibition rate （PIR） tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients.Results：High on-treatment platelet reactivity （HTPR） prevalence defined by PIR 〈30% by TEG in ADP-channel was 32.76% （38/116）.With respect to the normal wild type,CYP2C 19＊2,and ＊3 LOF alleles,and ＊ 17 GOF alleles,patients were classified into three metabolism phenotypes：41.38% were extensive metabolizers （EMs）,56.90% were intermediate metabolizers （IMs）,and 1.72% were poor metabolizers （PMs）.Of the enrolled patients,31.47%,5.17%,and 0.43%,respectively,were carriers of ＊2,＊3,and ＊ 17 alleles.The HTPR incidence differed significantly according to CYP2C 19 genotypes,accounting for 18.75%,41.54%,and 100.00% in EMs,IMs,and PMs,respectively.Eighteen （17.24%） ischemic events occurred during the 3-month follow-up,and there was a significant difference in ischemic events between HTPR group and nonhigh on-treatment platelet reactivity group.Conclusions：Genetic CYP2C 19 polymorphisms are relative to the inferior,the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS.

关 键 词：Acute Coronary Syndrome Clopidogrel Resistance CYP2C19 Polymorphisms Platelet Reactivity THROMBELASTOGRAPHY 

分 类 号：S512.103[农业科学—作物学] Q51[生物学—生物化学]