Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Clin Pharmacol Ther. 2012 Feb;91(2):257-63. doi: 10.1038/clpt.2011.221. Epub 2011 Dec 21.
Variants in ABCB1 and CYP2C19 have been identified as predictors of cardiac events during clopidogrel therapy initiated after myocardial infarction (MI) or percutaneous coronary intervention (PCI). In addition, PON1 has recently been associated with stent thrombosis. The reported effects of these variants have not yet been replicated in a real-world setting. We used BioVU, the Vanderbilt DNA repository linked to de-identified electronic health records (EHRs), to find data on patients who were on clopidogrel treatment after an MI and/or a PCI; among these, we identified those who had experienced one or more recurrent cardiac events while on treatment (cases, n = 225) and those who had not experienced any cardiac event while on treatment (controls, n = 468). We found that CYP2C19*2 (hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.16-2.06, P = 0.003) and ABCB1 (HR 1.28, 95% CI 1.04-1.57, P = 0.018), but not PON1 (HR 0.91, 95% CI 0.73-1.12, P = 0.370), were associated with recurrent events. In this population, genetic signals for clopidogrel resistance in ABCB1 and CYP2C19 were replicated, supporting the use of EHRs for pharmacogenomic studies. Our data do not show an association between PON1 and recurrent cardiovascular events.
ABCB1 和 CYP2C19 的变异被认为是心肌梗死 (MI) 或经皮冠状动脉介入治疗 (PCI) 后氯吡格雷治疗期间心脏事件的预测因子。此外，PON1 最近与支架血栓形成有关。这些变体的报告影响尚未在真实环境中得到复制。我们使用 BioVU，即与去识别电子健康记录 (EHR) 相关联的范德比尔特 DNA 存储库，寻找 MI 和/或 PCI 后接受氯吡格雷治疗的患者的数据；在这些患者中，我们确定了那些在治疗过程中经历了一次或多次复发性心脏事件的患者 (病例，n = 225) 和那些在治疗过程中没有经历任何心脏事件的患者 (对照，n = 468)。我们发现 CYP2C19*2（风险比 (HR) 1.54，95%置信区间 (CI) 1.16-2.06，P = 0.003）和 ABCB1（HR 1.28，95% CI 1.04-1.57，P = 0.018），但不是 PON1（HR 0.91，95% CI 0.73-1.12，P = 0.370），与复发性事件相关。在该人群中，ABCB1 和 CYP2C19 中氯吡格雷耐药的遗传信号得到了复制，支持使用 EHR 进行药物基因组学研究。我们的数据没有显示 PON1 与复发性心血管事件之间存在关联。
