Dai Ze-long, Chen Hui, Wu Xiao-ying
Department of Cardiovascular Diseases, Provincial Clinical College of Fujian Medical University, Fujian Provincial Institute of Cardiovascular Diseases, Fuzhou 350001, Fujian Province, China.
Zhong Xi Yi Jie He Xue Bao. 2012 Jun;10(6):647-54. doi: 10.3736/jcim20120608.
To assess the impact of cytochrome P450 (CYP) 2C19*17 allelic variant on platelet aggregation and bleeding risk in Chinese patients with blood stasis syndrome undergoing percutaneous coronary intervention (PCI) and treated with clopidogrel.
A total of 520 patients with blood stasis syndrome undergoing PCI after pretreatment with 300 mg clopidogrel and aspirin were studied from July 2009 to April 2011 in Fujian Provincial Institute of Cardiovascular Diseases. CYP2C19*17 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Platelet aggregation induced by 5μmol/L of adenosine diphosphate (ADP) was analyzed with platelet-rich plasma and platelet-poor plasma by turbidimetry method before and after 10 d of treatment with clopidogrel.
Bleeding events were observed in 5.96% of patients after thrombolysis for myocardial infarction, and the ratio of patients with CYP2C1917 allele was 7.98%. The bleeding rate in patients carrying CYP2C1917 allele, heterozygous (wt/*17) and homozygous (*17/17), was higher than that in patients with wild-type homozygotes (wt/wt) (P<0.01). At baseline, ADP-induced light transmission at maximal aggregation, 5-min aggregation and disaggregation showed no significant difference among patients with the three different CYP2C1917 genotypes. However, after 10-day administration of clopidogrel, values of ADP-induced platelet aggregation in *17/*17 and wt/*17 carriers were significantly decreased compared with the wild-type homozygotes (P<0.05, P<0.01); the inhibition rate of platelet aggregation was higher in patients carrying *17/*17 and wt/*17 than those only carrying wt/wt, and the same result was found in disaggregation of platelet after 10-day treatment (P<0.05, P<0.01). Patients with wt/*17 and *17/17 allele of CYP2C19 showed a higher risk of bleeding than those with wild-type allele (P<0.01), and the occurrence of bleeding was highest in patients with CYP2C1917 homozygotes.
CYP2C19*17 allele is associated with enhanced response to clopidogrel and an increased risk of bleeding in patients with blood stasis syndrome of coronary artery disease treated by clopidogrel.
评估细胞色素P450（CYP）2C19*17等位基因变异对接受经皮冠状动脉介入治疗（PCI）并使用氯吡格雷治疗的中国血瘀证患者血小板聚集和出血风险的影响。
2009年7月至2011年4月，在福建省心血管病研究所对520例接受PCI且在预处理时服用300mg氯吡格雷和阿司匹林的血瘀证患者进行研究。采用聚合酶链反应-限制性片段长度多态性方法测定CYP2C19*17基因型。用富含血小板血浆和乏血小板血浆，通过比浊法分析氯吡格雷治疗10天前后5μmol/L二磷酸腺苷（ADP）诱导的血小板聚集情况。
心肌梗死溶栓后5.96%的患者发生出血事件，携带CYP2C1917等位基因的患者比例为7.98%。携带CYP2C1917等位基因的杂合子（wt/*17）和纯合子（*17/17）患者的出血率高于野生型纯合子（wt/wt）患者（P<0.01）。基线时，三种不同CYP2C1917基因型患者的ADP诱导最大聚集时的透光率、5分钟聚集率和解聚率无显著差异。然而，氯吡格雷给药10天后，*17/*17和wt/17携带者的ADP诱导血小板聚集值与野生型纯合子相比显著降低（P<0.05，P<0.01）；携带17/*17和wt/*17的患者血小板聚集抑制率高于仅携带wt/wt的患者，10天治疗后血小板解聚情况也得到相同结果（P<0.05，P<0.01）。携带CYP2C19的wt/17和17/17等位基因的患者出血风险高于野生型等位基因患者（P<0.01），CYP2C1917纯合子患者出血发生率最高。
CYP2C19*17等位基因与氯吡格雷治疗的冠心病血瘀证患者对氯吡格雷反应增强及出血风险增加有关。
