Department of Cardiology, Epworth Hospital, Richmond, Melbourne, Australia.
Heart Lung Circ. 2011 Oct;20(10):657-8. doi: 10.1016/j.hlc.2010.06.1054. Epub 2011 Jan 6.
Clopidogrel is a widely used anti-platelet agent for the prevention of arterial thrombosis. Clopidogrel is administered as a pro-drug and metabolised to its active metabolite by the hepatic cytochrome P450 2C19 (CYP2C19) enzyme. The active metabolite is responsible for the anti-platelet activity of clopidogrel. Recent studies demonstrate that single nucleotide polymorphisms, (SNP's), in the gene for CYP2C19 result in significantly reduced production of the active metabolite of clopidogrel. Additional studies demonstrate that patients with SNP's in the CYP2C19 gene, including CYP2C19*2,*3,*4, and *5, have reduced production of the active metabolite of clopidogrel, reduced inhibition of platelet aggregation and increased incidence of coronary, cerebrovascular, and coronary stent thrombosis. We have been interested in determining the CYP2C19 genotype in cases of coronary stent thrombosis whilst on clopidogrel treatment and provide two case reports of coronary stent thrombosis whilst taking clopidogrel with subsequent CYP2C19 genotyping. As patients at risk of atherothrombosis in general, and stent thrombosis in particular, may be receiving or considered for anti-platelet therapy including clopidogrel, genotyping for CYP2C19 SNP's may be of benefit in the selection of appropriate anti-platelet therapy.
氯吡格雷是一种广泛用于预防动脉血栓形成的抗血小板药物。氯吡格雷作为前体药物给药，并通过肝细胞色素 P450 2C19（CYP2C19）酶代谢为其活性代谢物。活性代谢物负责氯吡格雷的抗血小板活性。最近的研究表明，CYP2C19 基因中的单核苷酸多态性（SNP）导致氯吡格雷的活性代谢物产生显著减少。其他研究表明，CYP2C19 基因中的 SNP 患者，包括 CYP2C19*2、*3、4 和5，氯吡格雷的活性代谢物产生减少，血小板聚集抑制减少，冠状动脉、脑血管和冠状动脉支架血栓形成的发生率增加。我们一直有兴趣在服用氯吡格雷治疗时确定冠状动脉支架血栓形成病例中的 CYP2C19 基因型，并提供两例服用氯吡格雷时发生冠状动脉支架血栓形成的病例报告，随后进行 CYP2C19 基因分型。由于一般存在动脉血栓形成风险的患者，特别是支架血栓形成的患者，可能正在接受或考虑接受包括氯吡格雷在内的抗血小板治疗，因此 CYP2C19 SNP 的基因分型可能有助于选择适当的抗血小板治疗。
