P2Y1、P2Y12和ITGB3基因多态性对PCI术后氯吡格雷抗血小板效应的影响

Association of P2Y1,P2Y12 and ITGB3 Genetic Polymorphisms with the Antiplatelet Efficacy of Aspirin and Clopidogrel after PCI

目的:观察P2Y1、P2Y12和ITGB3基因多态性对经皮冠状动脉介入(PCI)术后氯吡格雷抗血小板效应的影响。方法:520例冠心病患者行PCI术前给予硫酸氢氯吡格雷负荷剂量300 mg/d,口服+阿司匹林负荷剂量100 mg/d,口服;术后给予硫酸氢氯吡格雷维持剂量75 mg/d,口服,服用6个月以上+阿司匹林维持剂量100 mg/d,口服,服用1年,如患者出现胃出血等不宜服用时停止用药。观察患者一般资料、基因分型、P2Y1单体型与主要不良心血管事件(MACE)、出血事件的关联性。结果:520例患者中约82%为男性,40%为吸烟者;老年、合并高血压或合并糖尿病时MACE发生风险相对较高,风险比(HR,95%CI)分别为1.03(1.00,1.06)、3.15(1.46,6.78)和2.78(1.51,5.10);合并糖尿病可增加出血风险,服用血管紧张素转换酶(ACE)抑制剂可减少出血风险,比值比(OR,95%CI)分别为1.94(1.14,3.33)和0.51(0.30,0.84);P2Y12 c.-15+742C>T、P2Y1 c.57C>T、P2Y1 c.786A>G不同基因型及P2Y1不同单体型患者PCI术后MACE及出血事件比较,差异均无统计学意义(P>0.05)。ITGB3因最小等位基因频率较小,未作统计学分析。结论:P2Y1、P2Y12和ITGB3基因型不能作为冠心病患者临床终点事件和出血事件发生风险的标记物。

OBJECTIVE： To observe the association of P2Y1, P2Y12 and ITGB3 genetic polymorphisms with the antiplatelet efficacy of aspirin and clopidogrel after percutaneous coronary intervention （PCI）. METHODS： 520 patients with coronary artery disease received antiplatelet therapy of aspirin combined with clopidogrel after PCI. All patients were given clopidogrel hydrogen sulfate 300 mg/d and aspirin 100 mg/d orally before PCI. After PCI. they were continuously given clopidogrel hydrogen sulfate 75 mg/d orally for 6 months after PCI and aspirin 100 mg/d orally for 1 year~ stopped taking mendicine if the patients suffered fi-om gastrorrhagia and other discomlbrts. The relationship of general information of patients, genotype and P2YI haplotype with main ad- verse cardiovascular events （MACE） and bleeding event were observed. RESULTS： Among 520 patients, 82% were males and .10% were smokers. Older age combined with diabetes or hypertension was associated with a higher risk for MACE. Hazard ratios （ HR and 95%C1 ） were 1.05; （ 1.00, 1.06）, 3.15（1.46,6.78） and 2.78 （ 1.51,5.10） for older age, diabetes and hypertension, respectively. Diabetes was also significantly associated with the risk of bleeding while the use of ACEIs could decrease the risk of bleeding events with OR（95%CI） of 1.94（1.14±33） and 0.51（0.30,0.84）. There was no statistical significance in the impact of P2Y12 c.-15＋742C〉T, P2Y1 c.57C〉T and c.786A〉G on the risk of MACE and the occurrence of bleeding event after PCI （P〉0.05）. ITGB3 gene had not been analyed statistically due to low frequency. CONCLUSIONS： P2Y1, P2YI2 and ITGB3 genetic variants arc not good genetic markers to predict the risk of clinical endpoints in patients with coronary artery disease alter PCI.