Laboratory of Pharmacy, Zhongda Hospital, Southeast University, Nanjing, China.
Pharmacology. 2013;91(3-4):165-72. doi: 10.1159/000346736. Epub 2013 Feb 12.
BACKGROUND/AIMS: The study was conducted to assess the influence of CYP2C19 polymorphisms on clopidogrel response variability and recurrent cardiovascular (CV) events in Chinese patients undergoing percutaneous coronary intervention (PCI).
Platelet aggregation induced by 5 and 20 µmol/l adenosine diphosphate was measured in 109 patients at baseline, 12 h and 36 h after loading with 300 mg of clopidogrel. The primary end point was recurrent CV events, and the follow-up was scheduled at 1, 3, 6 and 12 months after PCI. The polymorphisms of CYP2C192 and CYP2C193 were genotyped by DNA sequencing analysis.
The maximal aggregation rates and inhibition of platelet aggregation among CYP2C19*1/1, CYP2C191/*2 or 3 and CYP2C192/2 or 3 genotypes were significantly different at 12 and 36 h after clopidogrel loading dose administration. Multiple linear regression analysis demonstrated that CYP2C192 and CYP2C193 might be predictors of clopidogrel response variability. During the 12-month follow-up, recurrent CV events occurred in 21 (19.63%) patients, and there were 5 (6.47%) deaths, 3 (2.80%) cases of ischemic stroke and 14 (13.1%) cases of acute coronary syndrome. Carriers of at least one CYP2C19 loss-of-function allele (*1/*2 or *3, *2/*2 or *3) incurred a 3.65-fold increase (95% CI 1.07-12.38; p = 0.038) in the risk of recurrent CV events 1 year after PCI compared to noncarriers (*1/*1).
Polymorphisms in CYP2C192 and CYP2C193 contribute to variabilities in clopidogrel responsiveness. Patients carrying at least one CYP2C19 loss-of-function allele (CYP2C19*2, *3) are associated with an increased risk of recurrent CV events undergoing PCI.
背景/目的：本研究旨在评估 CYP2C19 多态性对中国经皮冠状动脉介入治疗（PCI）患者氯吡格雷反应变异性和复发性心血管（CV）事件的影响。
在 109 例患者服用 300mg 氯吡格雷负荷剂量后 12 小时和 36 小时，测量由 5μmol/L 和 20μmol/L 二磷酸腺苷诱导的血小板聚集。主要终点为复发性 CV 事件，PCI 后 1、3、6 和 12 个月进行随访。通过 DNA 测序分析对 CYP2C192 和 CYP2C193 多态性进行基因分型。
在氯吡格雷负荷剂量给药后 12 小时和 36 小时，CYP2C19*1/1、CYP2C191/*2 或 3 和 CYP2C192/2 或 3 基因型之间的最大聚集率和血小板聚集抑制率存在显著差异。多元线性回归分析表明，CYP2C192 和 CYP2C193 可能是氯吡格雷反应变异性的预测因子。在 12 个月的随访期间，21 例（19.63%）患者发生复发性 CV 事件，5 例（6.47%）死亡，3 例（2.80%）缺血性卒中，14 例（13.1%）急性冠状动脉综合征。至少携带一个 CYP2C19 功能丧失等位基因（*1/*2 或 *3、*2/*2 或 *3）的患者与非携带者（*1/*1）相比，PCI 后 1 年复发性 CV 事件的风险增加 3.65 倍（95%CI 1.07-12.38；p=0.038）。
CYP2C192 和 CYP2C193 多态性导致氯吡格雷反应性变异性。携带至少一个 CYP2C19 功能丧失等位基因（CYP2C19*2、*3）的患者与 PCI 后复发性 CV 事件的风险增加相关。
