CYP2C19基因多态性对氯吡格雷药效的影响

Effect of CYP2C19 Gene Polymorphism on Antiplatelet Effect of Clopidogrel Therapy

氯吡格雷一种广泛应用的抗血小板聚集药物,在缺血性脑血管病二级预防中起着重要的作用。然而,在临床实践中不断发现,不同的患者对氯吡格雷的反应性差异比较大,某些患者对氯吡格雷的反应性较低或无反应,称之为氯吡格雷低反应或氯吡格雷抵抗,氯吡格雷的低反应或抵抗在缺血性脑血管病复发中起到重要的作用。参与氯吡格雷反应下降的因素有很多,包括基因的多态性(如细胞色素P450、ABCB1及P2Y12基因多态性)、药物的互相作用(质子泵抑制剂、他汀类等)、患者的依从性、Ⅱ型糖尿病、慢性肾病等,但目前机制尚未完全清楚。而CYP2C19作为细胞色素P450(CYP450)家族中一类重要的亚型,在多种药物代谢中体现出其重要性。氯吡格雷作为一种常见的抗血小板药物,其代谢也受CYP2C19基因多态性的影响,不同基因型患者对氯吡格雷的治疗反应性不同。文中就CYP2C19的几个主要基因多态性位点对氯吡格雷代谢的影响作综述。

Clopidogrel, an antiplatelet drug used extensively in clinic, plays an important role in the secondary prevention of ischemic cerebrovascular disease. However, in clinical practice, different clopidogrel response in different patients existed, some patients had low response or no response to clopidogrel, which is called clopidogrel hyporesponse or clopidogrel resistance and may lead to recurrence of ischemic cerebrovascular disease. Many factors, including gene polymorphism（such as cytochrome P450, ABCB1, P2Y12 and so on）, drug interaction（proton pump inhibitor and statins, etc.）, compliance of patients, type II diabetes mellitus and chronic kidney disease, etc. may take part in clopidogrel hyporesponse. The exact mechanism still remains incompletely understood. CYP2C19, as a significant subtype of cytochrome P450（CYP450） family, reflects essentiality in many drugs metabolism. As a common antiplatelet drug, clopidogrel＇s metabolism is also influenced by CYP2C19 gene polymorphism. Patients with different genetype have different response to clopidogrel. Several main CYP2C19 gene-locus and their impact on clopidogrel metabolism were reviewed.