Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, PR China.
PLoS One. 2013;8(3):e59344. doi: 10.1371/journal.pone.0059344. Epub 2013 Mar 12.
Several studies have indicated that CYP2C19 loss-of-function polymorphisms have a higher risk of stent thrombosis (ST) after percutaneous coronary interventions (PCIs). However, this association has not been investigated thoroughly in a Chinese population. In this study, we aimed to determine the effect of CYP2C192 and CYP2C193 loss-of-function polymorphisms on the occurrence of ST and other adverse clinical events in a Chinese population.
We designed a cohort study among 1068 consecutive patients undergoing intracoronary stent implantation after preloading with 600 mg of clopidogrel. CYP2C192 and CYP2C193 were genotyped by using polymerase chain reaction-restriction fragment length polymorphism analysis. The adverse clinical events recorded were ST, death, myocardial infarction (MI), and bleeding events. The primary end point of the study was the incidence of cumulative ST within 1 year after PCI. The secondary end point was other adverse clinical outcomes 1 year after the procedure.
The cumulative 1-year incidence of ST was 0.88% in patients with extensive metabolizers (EMs) (CYP2C19*1/1 genotype), 4.67% in patients with intermediate metabolizers (IMs) (CYP2C191/*2 or *1/3 genotype), and 10.0% in patients with poor metabolizers (PMs) (CYP2C192/*2, *2/*3, or *3/*3 genotype) (P<0.001). The one-year event-free survival was 97.8% in patients with EMs, 96.5% in patients with IMs, and 92.0% in patients with PMs (P = 0.014). Multivariate analysis confirmed the independent association of CYP2C19 loss-of-function allele carriage with ST (P = 0.009) and total mortality (P<0.05).
PM patients had an increased risk of ST, death, and MI after coronary stent placement in a Chinese population.
几项研究表明，CYP2C19 失活突变与经皮冠状动脉介入治疗（PCI）后支架血栓形成（ST）的风险较高有关。然而，这一关联在中国人群中尚未得到充分研究。本研究旨在确定 CYP2C192 和 CYP2C193 失活突变在中国人群中对 ST 及其他不良临床事件发生的影响。
我们对 1068 例接受 600mg 氯吡格雷负荷治疗后行冠状动脉内支架植入术的连续患者进行了队列研究。采用聚合酶链反应-限制性片段长度多态性分析方法对 CYP2C192 和 CYP2C193 进行基因分型。记录的不良临床事件包括 ST、死亡、心肌梗死（MI）和出血事件。研究的主要终点是 PCI 后 1 年内累积 ST 的发生率。次要终点是术后 1 年的其他不良临床结局。
广泛代谢者（EMs）（CYP2C19*1/1 基因型）患者 1 年累积 ST 发生率为 0.88%，中间代谢者（IMs）（CYP2C191/*2 或 *1/3 基因型）为 4.67%，弱代谢者（PMs）（CYP2C192/*2、*2/*3 或 *3/*3 基因型）为 10.0%（P<0.001）。EMs 患者 1 年无事件生存率为 97.8%，IMs 患者为 96.5%，PMs 患者为 92.0%（P=0.014）。多变量分析证实 CYP2C19 失活等位基因携带与 ST（P=0.009）和总死亡率（P<0.05）独立相关。
在中国人群中，PM 患者在冠状动脉支架置入后发生 ST、死亡和 MI 的风险增加。
