P2Y12基因变异对氯吡格雷联合阿司匹林治疗缺血性脑血管病患者血小板抑制率的影响

Impact of P2Y12 genetic polymorphism on the platelet inhibition in aspirin combined clopidogrel treatment for symptomatic extracranial or intracranial stenosis disease

目的探索P2Y12基因变异对缺血性脑血管病患者血小板抑制率的影响。方法入组症状性颅内动脉狭窄所致缺血性脑血管病患者(CYP2C19基因为野生型),通过连锁分析和功能预测筛选P2Y12基因的TagSNP和功能SNP位点,血栓弹力图检测血小板活性,统计分析基因变异对血小板活性的影响。结果最终入组患者188例,选择P2Y12基因的14个位点,进一步的连锁不平衡分析检测到两个连锁区域,第一个连锁区涵盖了4个SNP位点,第二个连锁区有9个位点。位点rs2046934对血栓弹力图参数ADP%和MAADP有显著影响(P <0.05)。结论通过检测P2Y12基因的位点rs2046934,有助于临床中筛查抗血小板药物抵抗患者。

Objective To determine the effect of P2 Y12 genetic variation on the platelet inhibition rate in patients with ischemic cerebrovascular disease. Methods Patients with ischemic cerebrovascular disease caused by symptomatic intracranial artery stenosis(CYP2 C19 gene being wild type) were recruited in this study. The TagSNP and functional SNP loci of P2 Y12 gene were screened by linkage disequilibrium(LD) analysis and functional prediction. Thrombelastography(TEG) was used to detect the platelet activity, and the effect of gene variation on platelet activity was analyzed. Results Totally 188 patients enrolled in this study, and 14 loci of P2 Y12 genes were selected. Two blocks were found by LD analysis: the first block covering 4 SNP loci and the second 9 loci. The rs2046934 had a significant impact on TEG parameters ADP% and MAADP(P < 0.05). Conclusion Detecting the loci rs2046934 of P2 Y12 genes is helpful to screen antiplatelet drug resistance in patients.