Department of Clinical Pharmacy, St Antonius Hospital, PO Box 2500, Nieuwegein 3430 EM, The Netherlands.
Eur Heart J. 2010 Dec;31(24):3046-53. doi: 10.1093/eurheartj/ehq321. Epub 2010 Sep 10.
despite treatment with clopidogrel on top of aspirin, stent thrombosis (ST) still occurs being the most serious complication after percutaneous coronary interventions (PCIs). In this study, we aimed to determine the effect of variations in genes involved in the absorption (ABCB1 C1236T, G2677T/A, C3435T), metabolism (CYP2C192 and 3, CYP2C92 and 3, CYP3A41B and CYP3A53), and pharmacodynamics (P2Y1 A1622G) of clopidogrel on the occurrence of ST.
the selected genetic variants were assessed in 176 subjects who developed ST while on dual antiplatelet therapy with aspirin and clopidogrel and in 420 control subjects who did not develop adverse cardiovascular events, including ST, within 1 year after stenting. The timing of the definite ST was acute in 66, subacute in 87, and late in 23 cases. The presence of the CYP2C192 and CYP2C93 variant alleles was significantly associated with ST (OR(adj): 1.7, 95% CI: 1.0-2.6, P = 0.018 and OR(adj): 2.4, 95% CI: 1.0-5.5, P = 0.043, respectively). The influence of CYP2C192 (OR(adj): 2.5, 95% CI: 1.1-5.5, P = 0.026) and CYP2C93 (OR(adj): 3.3, 95% CI: 1.1-9.9, P = 0.031) was most strongly associated with subacute ST. No significant associations of the other genetic variations and the occurrence of ST were found.
carriage of the loss-of-function alleles CYP2C192 and CYP2C93 increases the risk on ST after PCI.
尽管在阿司匹林基础上加用氯吡格雷治疗，但支架血栓形成（ST）仍然是经皮冠状动脉介入治疗（PCI）后最严重的并发症。本研究旨在确定氯吡格雷吸收（ABCB1 C1236T、G2677T/A、C3435T）、代谢（CYP2C192 和3、CYP2C92 和3、CYP3A41B 和 CYP3A53）和药效学（P2Y1 A1622G）相关基因变异对 ST 发生的影响。
在 176 例接受阿司匹林和氯吡格雷双联抗血小板治疗后发生 ST 的患者和 420 例在支架置入后 1 年内未发生不良心血管事件（包括 ST）的对照组患者中评估了所选的遗传变异。明确 ST 的时间为急性 66 例，亚急性 87 例，晚期 23 例。CYP2C192 和 CYP2C93 变异等位基因的存在与 ST 显著相关（OR（adj）：1.7，95%CI：1.0-2.6，P=0.018 和 OR（adj）：2.4，95%CI：1.0-5.5，P=0.043）。CYP2C192（OR（adj）：2.5，95%CI：1.1-5.5，P=0.026）和 CYP2C93（OR（adj）：3.3，95%CI：1.1-9.9，P=0.031）的影响与亚急性 ST 关系最密切。未发现其他遗传变异与 ST 发生的显著相关性。
携带失活等位基因 CYP2C192 和 CYP2C93 会增加 PCI 后 ST 的风险。
