Abstract:
Aspirin resistance (AR) is a pressing problem in current ischemic stroke care. Although the role of genetic variations is widely considered, the data still remain controversial. Our aim was to investigate the contribution of genetic features to laboratory AR measured through platelet aggregation with arachidonic acid (AA) and adenosine diphosphate (ADP) in ischemic stroke patients. A total of 461 patients were enrolled. Platelet aggregation was measured via light transmission aggregometry. Eighteen single-nucleotide polymorphisms (SNPs) in ITGB3, GPIBA, TBXA2R, ITGA2, PLA2G7, HMOX1, PTGS1, PTGS2, ADRA2A, ABCB1 and PEAR1 genes and the intergenic 9p21.3 region were determined using low-density biochips. We found an association of rs1330344 in the PTGS1 gene with AR and AA-induced platelet aggregation. Rs4311994 in ADRA2A gene also affected AA-induced aggregation, and rs4523 in the TBXA2R gene and rs12041331 in the PEAR1 gene influenced ADP-induced aggregation. Furthermore, the effect of rs1062535 in the ITGA2 gene on NIHSS dynamics during 10 days of treatment was found. The best machine learning (ML) model for AR based on clinical and genetic factors was characterized by AUC = 0.665 and F1-score = 0.628. In conclusion, the association study showed that PTGS1, ADRA2A, TBXA2R and PEAR1 polymorphisms may affect laboratory AR. However, the ML model demonstrated the predominant influence of clinical features.
摘要:
阿司匹林抵抗(AR)是当前缺血性中风护理中的紧迫问题。虽然遗传变异的作用被广泛认为,数据仍然存在争议。我们的目的是研究遗传特征对缺血性中风患者通过花生四烯酸(AA)和二磷酸腺苷(ADP)的血小板聚集测量的实验室AR的贡献。共纳入461例患者。血小板聚集通过光透射聚集测定法测量。ITGB3,GPIBA,TBXA2R,ITGA2,PLA2G7,HMOX1,PTGS1,PTGS2,ADRA2A,使用低密度生物芯片确定ABCB1和PEAR1基因以及基因间9p21.3区域。我们发现PTGS1基因中的rs1330344与AR和AA诱导的血小板聚集有关。ADRA2A基因中的Rs4311994也影响AA诱导的聚集,TBXA2R基因中的rs4523和PEAR1基因中的rs12041331影响了ADP诱导的聚集。此外,发现ITGA2基因rs1062535在治疗10天期间对NIHSS动力学的影响。基于临床和遗传因素的AR的最佳机器学习(ML)模型的特征为AUC=0.665,F1评分=0.628。总之,关联研究表明,PTGS1、ADRA2A、TBXA2R和PEAR1多态性可能影响实验室AR。然而,ML模型显示了临床特征的主要影响.