Zhang Suli, Zhu Jinhang, Li Hua, Wang Lei, Niu Jiamin, Zhu Bin, He Lin, Shen Lu, Qin Shengying, Fang Shuxin
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Cardiology. 2018;140(1):21-29. doi: 10.1159/000488101. Epub 2018 Apr 10.
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.
Patients with inhibition of platelet aggregation (IPA) < 30% after treatment were classified as the high platelet reactivity (HPR) group. Patients with 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 Mass-ARRAY platform.
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).
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.
基因变异被认为是导致个体间血小板功能存在显著差异的原因,因此迫切需要鉴定可用于预测治疗反应的基因标志物。我们的研究调查了PEAR1、P2Y12和UGT2A1基因多态性是否与中国急性冠状动脉综合征患者双联抗血小板治疗后的血小板反应性相关。
治疗后血小板聚集抑制率(IPA)<30%的患者被归类为高血小板反应性(HPR)组。IPA>30%的患者被归类为正常血小板反应性(NPR)组。通过血栓弹力图(TEG)血小板功能检测法测量二磷酸腺苷(ADP)诱导的血小板聚集。使用Mass-ARRAY平台对PEAR1、P2Y12和UGT2A1的13个单核苷酸多态性(SNP)进行基因分型。
单因素分析显示,7个SNP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和rs11249454位点的次要等位基因C与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和rs7634096位点的次要等位基因T与NPR显著相关。在我们的研究中,发生复发性缺血事件的患者的平均IPA显著低于未发生复发性事件的患者(p = 0.048)。
我们的研究结果表明,PEAR1、P2Y12和UGT2A1基因变异可能是潜在的生物标志物,可用于指导氯吡格雷和阿司匹林在中国患者中的临床应用。