Supplementary Material for: Study of the Association of PEAR1, P2Y12, and UGT2A1 Polymorphisms with Platelet Reactivity in Response to Dual Antiplatelet Therapy in Chinese Patients

Objectives: Genetic variation is thought to contribute to considerable interindividual variability in platelet function, and there is a pressing need to identify genetic markers that can be used to predict the response to treatment. Our study investigated whether PEAR1, P2Y12, and UGT2A1 polymorphisms were associated with platelet reactivity in response to dual antiplatelet therapy in Chinese patients with acute coronary syndrome. Methods: Patients with inhibition of platelet aggregation (IPA) 30% were classified as the normal platelet reactivity (NPR) group. ADP-induced platelet aggregation was measured by thromboelastography (TEG) platelet-mapping assay. Thirteen single nucleotide polymorphisms (SNPs) of PEAR1, P2Y12 and UGT2A1 were genotyped using the Mass­ARRAY platform. Results: Seven SNPs were significantly associated with ADP-induced platelet aggregation by univariate analysis. Major allele G at rs12041331, minor allele G at rs2644592, minor allele C at rs11264580, and minor allele C at rs11249454 were significantly associated with HPR, whereas minor allele T at rs57731889, minor allele A at rs16863356, and minor allele T at rs7634096 were significantly associated with NPR. The mean IPA was significantly lower in patients suffering recurrent ischemic events than in patients without recurrent events in our study (p = 0.048). Conclusions: Our findings suggest that PEAR1, P2Y12, and UGT2A1 genetic variants may be potential biomarkers that can be used to guide clinical applications of clopidogrel and aspirin in Chinese patients.研究目的：遗传变异被认为是导致血小板功能存在显著个体间差异的关键因素，当前亟需筛选可用于预测治疗反应的遗传标志物。本研究旨在探讨中国急性冠脉综合征（acute coronary syndrome, ACS）患者中，PEAR1、P2Y12及UGT2A1基因多态性是否与双联抗血小板治疗后的血小板反应性相关。 研究方法：将血小板聚集抑制率（inhibition of platelet aggregation, IPA）为30%的患者归类为正常血小板反应性（normal platelet reactivity, NPR）组。采用血栓弹力图（thromboelastography, TEG）血小板图谱分析法检测ADP诱导的血小板聚集水平。采用MassARRAY平台对PEAR1、P2Y12及UGT2A1基因的13个单核苷酸多态性（single nucleotide polymorphisms, SNPs）进行基因分型。 研究结果：单变量分析显示，7个SNPs与ADP诱导的血小板聚集显著相关。rs12041331位点的主要等位基因G、rs2644592位点的次要等位基因G、rs11264580位点的次要等位基因C及rs11249454位点的次要等位基因C均与高血小板反应性（high platelet reactivity, HPR）显著相关；而rs57731889位点的次要等位基因T、rs16863356位点的次要等位基因A及rs7634096位点的次要等位基因T均与正常血小板反应性（NPR）显著相关。本研究中，发生复发性缺血事件的患者的平均IPA值显著低于未发生复发性事件的患者（p=0.048）。 研究结论：本研究结果表明，PEAR1、P2Y12及UGT2A1基因变异或可作为潜在的生物标志物，用于指导中国ACS患者应用氯吡格雷与阿司匹林的临床治疗方案。