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PEAR1基因变异与接受PCI治疗的ACS和稳定型CAD患者的预后相关。

Variants of PEAR1 Are Associated With Outcome in Patients With ACS and Stable CAD Undergoing PCI.

作者信息

Stimpfle Fabian, Bauer Maike, Rath Dominik, Schaeffeler Elke, Schwab Matthias, Gawaz Meinrad, Winter Stefan, Geisler Tobias

机构信息

Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany.

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.

出版信息

Front Pharmacol. 2018 May 15;9:490. doi: 10.3389/fphar.2018.00490. eCollection 2018.

Abstract

Platelet endothelial aggregation receptor 1 (PEAR1) triggers platelet aggregation and is expressed in platelets and endothelial cells. Genome-wide association studies (GWAS) showed an association between platelet function and single-nucleotide polymorphisms (SNPs) in . In 582 consecutive patients with stable coronary artery disease (CAD) or acute coronary syndrome (ACS) scheduled for PCI and treated with ASA and Clopidogrel, Prasugrel, or Ticagrelor, SNP analysis for rs12566888, rs2768759, rs41273215, rs3737224, and rs822442 was performed. During a follow-up period of 365 days after initial PCI, all patients were tracked for a primary endpoint, defined as a combined endpoint consisting of either time to death, myocardial infarction (MI) or ischemic stroke. All cause mortality, MI and ischemic stroke were defined as secondary endpoints. Multivariable Cox model analysis for the primary endpoint revealed a significantly increased risk in homozygous rs2768759 minor allele carriers (hazard ratio, 3.16; 95% confidence interval, 1.4-7.13, = 0.006). Moreover, rs12566888 minor allele carriers also showed an increased risk in all patients (hazard ratio, 1.69; 95% confidence interval, 0.87-3.27, = 0.122), which was marginally significant in male patients (hazard ratio, 2.12; 95% confidence interval, 1.02-4.43, = 0.045; = 425). To the best of our knowledge, this is the first study showing that distinct genetic variants of are associated with cardiovascular prognosis in high risk patients undergoing PCI and treated with dual anti platelet therapy.

摘要

血小板内皮聚集受体1(PEAR1)可触发血小板聚集,在血小板和内皮细胞中表达。全基因组关联研究(GWAS)表明血小板功能与[具体基因名称未给出]中的单核苷酸多态性(SNP)之间存在关联。在582例计划接受PCI并接受阿司匹林和氯吡格雷、普拉格雷或替格瑞洛治疗的连续性稳定冠状动脉疾病(CAD)或急性冠状动脉综合征(ACS)患者中,对rs12566888、rs2768759、rs41273215、rs3737224和rs822442进行了SNP分析。在初次PCI后的365天随访期内,对所有患者追踪主要终点,该终点定义为包括死亡时间、心肌梗死(MI)或缺血性卒中的复合终点。全因死亡率、MI和缺血性卒中被定义为次要终点。对主要终点的多变量Cox模型分析显示,纯合子rs2768759次要等位基因携带者的风险显著增加(风险比,3.16;95%置信区间,1.4 - 7.13,P = 0.006)。此外,rs12566888次要等位基因携带者在所有患者中也显示出风险增加(风险比,1.69;95%置信区间,0.87 - 3.27,P = 0.122),在男性患者中具有边缘显著性(风险比,2.12;95%置信区间,1.02 - 4.43,P = 0.045;n = 425)。据我们所知,这是第一项表明[具体基因名称未给出]的不同基因变异与接受PCI并接受双联抗血小板治疗的高危患者心血管预后相关的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae6d/5962768/e1af46b0173f/fphar-09-00490-g0001.jpg

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