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COX-2 rs20417 与阿司匹林抵抗的相关性。

Association of COX-2 rs20417 with aspirin resistance.

机构信息

Department of Molecular Biology, Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500016, India.

出版信息

J Thromb Thrombolysis. 2013 Jan;35(1):95-9. doi: 10.1007/s11239-012-0777-8.

Abstract

Aspirin is the most commonly used antiplatelet drug for treatment of a serious vascular event, most notably stroke and myocardial infarction. However, despite the demonstrated benefit of aspirin, significant fraction of aspirin-treated patients may be resistant to the antiplatelet effects of the drug. The possible mechanisms of aspirin resistance (AR) are multifactorial. A genetic basis for AR has been suggested to exist. Therefore, the present study was taken up to investigate the role of -765G/C polymorphism (rs20417) in the cyclooxygenase-2 (COX-2) gene with AR in stroke patients. Four hundred and fifty stroke patients and four hundred and forty age and sex matched healthy controls were involved in the study. Baseline clinical data were collected and follow-up telephone interviews were conducted with patients at 3 months post event to determine stroke outcome using Modified Rankin Scale. Blood samples were collected and genotypes determined by polymerase chain reaction-restriction digestion technique. The association between the genotypes and outcome was evaluated by stepwise multiple logistic regression analysis. The COX-2 CC and GC genotype showed a significant association with bad outcome. Therefore, the carriers of C allele of COX-2 -765G/C polymorphism are more prone to AR in comparison with non-carriers. These results support a potential role of -765G/C COX-2 gene polymorphism with AR in ischemic stroke patients.

摘要

阿司匹林是治疗严重血管事件(尤其是中风和心肌梗死)最常用的抗血小板药物。然而,尽管阿司匹林已被证明具有益处,但相当一部分接受阿司匹林治疗的患者可能对药物的抗血小板作用产生抵抗。阿司匹林抵抗(AR)的可能机制是多因素的。已经有人提出 AR 存在遗传基础。因此,本研究旨在探讨环氧化酶-2(COX-2)基因中-765G/C 多态性(rs20417)与中风患者 AR 之间的关系。本研究纳入了 450 名中风患者和 440 名年龄和性别匹配的健康对照者。收集基线临床数据,并在事件发生后 3 个月对患者进行电话随访,使用改良 Rankin 量表确定中风结局。采集血样,采用聚合酶链反应-限制性酶切技术确定基因型。通过逐步多因素逻辑回归分析评估基因型与结局之间的关系。COX-2 CC 和 GC 基因型与不良结局显著相关。因此,与非携带者相比,COX-2-765G/C 多态性的 C 等位基因携带者更容易发生 AR。这些结果支持 COX-2-765G/C 基因多态性与缺血性中风患者 AR 之间存在潜在作用。

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