Li Zhizhang, Jiang Huayu, Ding Ying, Zhang Dong, Zhang Xiaoguang, Xue Jie, Ma Ruinan, Hu Liang, Yue Yunhua
Department of Neurology, Yangpu Hospital Tongji University School of Medicine, Shanghai, China.
Front Cardiovasc Med. 2021 Sep 1;8:664012. doi: 10.3389/fcvm.2021.664012. eCollection 2021.
The role of genetic polymorphisms is important in defining the patient's prognosis and outcomes in coronary artery disease. The present study aimed to explore the association between platelet endothelial aggregation receptor 1 (PEAR1) rs12041331 polymorphism and the outcomes in patients with acute ischemic stroke treated with aspirin or dual antiplatelet therapy (DAPT) with clopidogrel. A total of 868 ischemic stroke patients admitted to our hospital from January 1, 2016 to December 30, 2018 were retrospectively studied. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification defined stroke subtypes. These patients were treated with aspirin alone or DAPT. The genotype distribution of PEAR1 rs12041331 single-nucleotide polymorphism (AA, AC, and CC) between different TOAST subtypes and treatment groups was assessed, and the clinical impact of genetic variants on functional outcomes defined by the National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthel Index was analyzed using univariate and multivariate logistic regression models. Among the 868 stroke patients, the PEAR1 AA genotype was 16%, GA was 47%, and GG was 36%. Forty-four percent had aspirin alone, and 56% had DAPT. Overall, the distribution of PEAR single-nucleotide polymorphism was not significant among the two treatment groups or subtypes of TOAST. In contrast, in patients treated with aspirin alone, PEAR1 AA tended to be higher in the small-artery occlusion (SAO) subtype when compared with the no-lacunar subtype, including cardioembolism and large-artery atherosclerosis. PEAR1 AA genotype was significantly associated with favorable functional outcomes at day 7 and discharge only in SAO patients treated with aspirin alone compared with the GG genotype. Multivariate regression models further suggested that AA genotype was independently associated with favorable outcomes in this group after being adjusted for three common stroke risk factors such as age, hypertension history, and C-reactive protein level [odds ratio (OR) 0.23, 95% confidence interval (CI), 0.07-0.64, = 0.02 for 7-day National Institutes of Health Stroke Scale; OR 0.2, 95% CI, 0.06-0.66, = 0.03 for 7-day modified Rankin Scale, and OR 0.25, 95% CI, 0.08-0.72, = 0.03 for 7-day Barthel Index, respectively]. The impact of PEAR1 rs12041331 polymorphism on aspirin depends on the TOAST subtype. PEAR1 AA carrier with SAO stroke is most sensitive to aspirin therapy. PEAR1 AA is an independent factor for the short-term functional outcomes in SAO patients treated with aspirin alone. 1800019911.
基因多态性在确定冠心病患者的预后和结局方面具有重要作用。本研究旨在探讨血小板内皮聚集受体1(PEAR1)rs12041331多态性与接受阿司匹林或阿司匹林联合氯吡格雷双重抗血小板治疗(DAPT)的急性缺血性脑卒中患者结局之间的关联。对2016年1月1日至2018年12月30日期间我院收治的868例缺血性脑卒中患者进行回顾性研究。急性卒中治疗中Org 10172试验(TOAST)分类定义了卒中亚型。这些患者接受了单独阿司匹林治疗或DAPT治疗。评估了不同TOAST亚型和治疗组之间PEAR1 rs12041331单核苷酸多态性(AA、AC和CC)的基因型分布,并使用单因素和多因素逻辑回归模型分析了基因多态性对由美国国立卫生研究院卒中量表、改良Rankin量表和Barthel指数定义的功能结局的临床影响。在868例卒中患者中,PEAR1 AA基因型占16%,GA占47%,GG占36%。44%的患者接受单独阿司匹林治疗,56%的患者接受DAPT治疗。总体而言,PEAR单核苷酸多态性在两个治疗组或TOAST亚型之间的分布无显著差异。相比之下,在单独接受阿司匹林治疗的患者中,与非腔隙性亚型(包括心源性栓塞和大动脉粥样硬化)相比,小动脉闭塞(SAO)亚型中PEAR1 AA的比例往往更高。与GG基因型相比,仅在单独接受阿司匹林治疗的SAO患者中,PEAR1 AA基因型与第7天和出院时良好的功能结局显著相关。多因素回归模型进一步表明,在调整年龄、高血压病史和C反应蛋白水平等三个常见卒中危险因素后,AA基因型与该组的良好结局独立相关[美国国立卫生研究院卒中量表第7天的比值比(OR)为0.23,95%置信区间(CI)为0.07 - 0.64,P = 0.02;改良Rankin量表第7天的OR为0.2,95% CI为0.06 - 0.66,P = 0.03;Barthel指数第7天的OR为0.25,95% CI为0.08 - 0.72,P = 0.03]。PEAR1 rs12041331多态性对阿司匹林的影响取决于TOAST亚型。SAO卒中的PEAR1 AA携带者对阿司匹林治疗最敏感。PEAR1 AA是单独接受阿司匹林治疗的SAO患者短期功能结局的独立因素。1800019911。