全基因组关联分析和细胞研究提示PEAR1受体参与血小板聚集、新生血管的形成，但它的作用和机理均未阐明。申请人前期研究发现PEAR1基因多态性与抗血小板药物药效相关，还与经皮冠状动脉介入治疗术后的支架内血栓和狭窄相关。据此，申请者推测PEAR1可能通过影响血小板功能、血管内皮细胞功能对抗血小板药物疗效产生至关重要的影响，并可能是潜在的抗血栓新靶点。本项目中我们用已构建的PEAR1基因敲除小鼠模型，模拟PEAR1拮抗或功能缺失的情况，与野生型小鼠比较抗血小板药物作用下血小板聚集、血栓形成，同时测定PEAR1及下游细胞信号因子磷酸化以证明机理；最后用已建立的患者样本库，采用二代测序技术测定PEAR1及相关基因的全序列，分析PEAR1与相关基因的协同作用。本研究将探索PEAR1作为抗血栓药理学新靶点的可能，并有望发现基因导向个体化治疗新位点。

The genome-wide association studies (GWAS) and cell researches verified the important role of Platelet endothelial aggregation receptor-1 (PEAR1) on platelet reaction and neovascularization. Our previous studies found PEAR1 genetic polymorphisms influenced pharmacodynamics of antiplatelet drugs. Therefore, we hypothesis that PEAR1 probably have a critical effect on antiplatelet drugs’ efficacy, due to its influence on platelet and endothelial cells function. In the present study, based on the established PEAR1 knockout mice model which simulates PEAR1 inhibition or function loss, we compared the Pear1 knockout mice with the wild mice of thrombosis. To clarify the mechanism, we will also detect the phosphorylation of PEAR1 and cell single factors. Finally, to investigate the association between PEAR1 SNPs and SNPs on other related genes, we use next generation sequencing technology to detect these SNPs and evaluate their effects on antiplatelet durgs therapy.