Yi Xingyang, Han Zhao, Zhou Qiang, Lin Jing, Wang Chun
Department of Neurology, People's Hospital of Deyang City, 173 North Taishan Road, Deyang, Sichuan 618000, China.
Department of Neurology, The 2nd affiliated hospital and Yuying children hospital of Wenzhou Medical University, No 109, Xueyuan West Road, Wenzhou, Zhejiang 325027, China.
Ther Adv Neurol Disord. 2017 Mar;10(3):161-170. doi: 10.1177/1756285616681943. Epub 2016 Dec 1.
The effect of gene variants and their interactions on response to aspirin and clinical adverse outcomes after an acute ischemic stroke (IS) is not fully understood. The aim of this study was to investigate the association of aspirin-relevant gene variants and their interactions with clinical adverse outcomes in IS patients taking aspirin.
A total of 14 variants from six genes encoding COX enzymes (), platelet membrane receptors () and glycoprotein receptor were examined in 850 acute IS patients. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients were followed up for 1 year after admission. Primary outcome was a composite of recurrent ischemic stroke (RIS), myocardial infarction (MI) and death.
The primary outcome occurred in 112 (13.5%) patients (81 RIS, 16 MI and 15 deaths). There were no significant differences in the frequencies of the genotypes of the 14 variants between the patients with and without primary outcome using single-locus analytical approach. However, there was significant gene-gene interaction among rs20417, rs1371097 and rs2317676. The high-risk interactive genotypes of rs20417, rs1371097 and rs2317676 were independently associated with primary adverse outcome of RIS, MI, and death after acute IS.
The three-loci interactions are associated with sensitivity of IS patients to aspirin and aspirin-induced adverse clinical events. The combinatorial analysis used in this study may be helpful to elucidate complex genetic risk of aspirin resistance (AR).
The study described here is registered at http://www.chictr.org/ (unique identifier: ChiCTR-OCH-14004724).
基因变异及其相互作用对急性缺血性卒中（IS）后阿司匹林反应及临床不良结局的影响尚未完全明确。本研究旨在探讨服用阿司匹林的IS患者中与阿司匹林相关的基因变异及其相互作用与临床不良结局的关联。
在850例急性IS患者中检测了6个编码COX酶、血小板膜受体和糖蛋白受体的基因中的14个变异。采用广义多因素降维分析（GMDR）分析基因-基因相互作用。所有患者入院后随访1年。主要结局为复发性缺血性卒中（RIS）、心肌梗死（MI）和死亡的复合结局。
112例（13.5%）患者出现主要结局（81例RIS，16例MI和15例死亡）。采用单基因座分析方法，有和无主要结局的患者中14个变异的基因型频率无显著差异。然而，rs20417、rs1371097和rs2317676之间存在显著的基因-基因相互作用。rs20417、rs1371097和rs2317676的高危交互基因型与急性IS后RIS、MI和死亡的主要不良结局独立相关。
三位点相互作用与IS患者对阿司匹林的敏感性及阿司匹林诱导的不良临床事件相关。本研究中使用的组合分析可能有助于阐明阿司匹林抵抗（AR）的复杂遗传风险。
本文所述研究已在http://www.chictr.org/注册（唯一标识符：ChiCTR-OCH-14004724）。
