CYP2C19*2 and Other Allelic Variants Affecting Platelet Response to Clopidogrel Tested by Thrombelastography in Patients with Acute Coronary Syndrome.
CYP2C19*2 and Other Allelic Variants Affecting Platelet Response to Clopidogrel Tested by Thrombelastography in Patients with Acute Coronary Syndrome.
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DOI：
10.4103/0366-6999.162515
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发表时间：
2015-08-20
影响因子：
6.1
通讯作者：
Wang WM
中科院分区：
文献类型：
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作者：
Liu J;Nie XY;Zhang Y;Lu Y;Shi LW;Wang WM
探讨中国急性冠脉综合征（ACS）患者中CYP 2C 19基因多态性对血栓弹力图（TEG）检测的各种氯吡格雷反应的影响。前瞻性筛选ACS诊断患者，并给予氯吡格雷和阿司匹林双重抗血小板治疗。对116例患者的CYP 2C 19功能丧失（LOF）和功能获得（GOF）基因型、TEG法测定的腺苷二磷酸（ADP）通道血小板抑制率（PIR）以及3个月内主要心血管不良事件和缺血性事件的发生情况进行了评估。治疗中血小板高反应性（HTPR）的患病率为32.76%（38/116），定义为ADP通道TEG的PIR <30%。根据正常野生型、CYP 2C 19 *2和 *3 LOF等位基因以及 *17 GOF等位基因，将患者分为3种代谢表型：41.38%为快代谢型（EM），56.90%为中代谢型（IM），1.72%为慢代谢型（PM）。在入组患者中，分别有31.47%、5.17%和0.43%为 *2、*3和 *17等位基因携带者。不同CYP 2C 19基因型HTPR的发生率差异有统计学意义，EM、IM和PM中HTPR的发生率分别为18.75%、41.54%和100.00%。3个月随访期间发生18例（17.24%）缺血事件，HTPR组与非高血小板反应性组之间的缺血事件差异有统计学意义。CYP 2C 19基因多态性与ACS患者服用氯吡格雷后抗血小板活性降低有关，并可能增加ACS患者缺血性事件的发生率。
To investigate the contributions of CYP2C19 polymorphisms to the various clopidogrel responses tested by thrombelastography (TEG) in Chinese patients with the acute coronary syndrome (ACS). Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy. CYP2C19 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. 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, CYP2C19*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 CYP2C19 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. Genetic CYP2C19 polymorphisms are relative to the inferior, the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS.