PDF(Pubmed)
Abstract：
A recently discovered haplotype-CYP2C:TG-determines the ultrarapid metabolism of several CYP2C19 substrates. The platelet inhibitor clopidogrel requires CYP2C19-mediated activation: the risk of ischemic events is increased in patients with a poor (PM) or intermediate (IM) CYP2C19 metabolizer phenotype (vs. normal, NM; rapid, RM; or ultrarapid, UM). We investigated whether the CYP2C:TG haplotype affected efficacy/bleeding risk in clopidogrel-treated patients. Adults (n = 283) treated with clopidogrel over 3-6 months were classified by CYP2C19 phenotype based on the CYP2C19*2*17 genotype, and based on the CYP2C19/CYP2C cluster genotype, and regarding carriage of the CYP2:TG haplotype, and were balanced on a number of covariates across the levels of phenotypes/haplotype carriage. Overall, 45 (15.9%) patients experienced ischemic events, and 49 (17.3%) experienced bleedings. By either classification, the incidence of ischemic events was similarly numerically higher in PM/IM patients (21.6%, 21.8%, respectively) than in mutually similar NM, RM, and UM patients (13.2-14.8%), whereas the incidence of bleeding events was numerically lower (13.1% vs. 16.6-20.5%). The incidence of ischemic events was similar in CYP2C:TG carries and non-carries (14.1% vs. 16.1%), whereas the incidence of bleedings appeared mildly lower in the former (14.9% vs. 20.1%). We observed no signal to suggest a major effect of the CYP2C19/CYP2C cluster genotype or CYP2C:TG haplotype on the clinical efficacy/safety of clopidogrel.
摘要：
最近发现的单倍型-CYP2C：TG-决定了几种CYP2C19底物的超快速代谢。血小板抑制剂氯吡格雷需要CYP2C19介导的激活：患有不良（PM）或中等（IM）CYP2C19代谢表型的患者发生缺血事件的风险增加（与正常,NM；快速，RM；或超短，um).我们调查了CYP2C：TG单倍型是否影响氯吡格雷治疗患者的疗效/出血风险。使用氯吡格雷治疗3-6个月的成人（n=283）根据CYP2C19*2*17基因型进行CYP2C19表型分类，基于CYP2C19/CYP2C簇基因型，关于CYP2：TG单倍型的携带，并且在表型/单倍型携带水平的多个协变量上保持平衡。总的来说,45例（15.9%）患者发生缺血事件，49人(17.3%)出现出血。无论是哪种分类，在PM/IM患者中，缺血事件的发生率同样在数值上较高(21.6%，21.8%,分别)比在相互相似的NM中，RM,和UM患者（13.2-14.8%），而出血事件的发生率在数字上较低(13.1%vs.16.6-20.5%）。CYP2C中缺血事件的发生率相似：TG携带和非携带（14.1%vs.16.1%），而前者的出血发生率则稍低(14.9%vs.20.1%）。我们没有观察到表明CYP2C19/CYP2C簇基因型或CYP2C：TG单倍型对氯吡格雷临床疗效/安全性有重大影响的信号。
