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心血管疾病的药物基因组学:以阿司匹林和 ADP 受体拮抗剂为例。

Pharmacogenomics in cardiovascular disease: focus on aspirin and ADP receptor antagonists.

机构信息

Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.

出版信息

J Thromb Haemost. 2013 Sep;11(9):1627-39. doi: 10.1111/jth.12318.

Abstract

Antiplatelet agents like aspirin and adenosine diphosphate receptor antagonists are effective in reducing recurrent ischemic events. Considerable inter-individual variability in the platelet inhibition obtained with these drugs has initiated a search for explanatory mechanisms and ways to improve treatment. In recent years, numerous genetic polymorphisms have been linked with reduced platelet inhibition and lack of clinical efficacy of antiplatelet drugs, particularly clopidogrel and aspirin. Consequently, attempts to adjust antiplatelet treatment according to genotype have been made, but the clinical benefit has been modest in studies performed so far. The progress in genome science over the last decade and the declining cost of sequencing technologies hold the promise of enabling genetically tailored antiplatelet therapy. However, more evidence is needed to clarify which polymorphisms may serve as targets to improve treatment. The present review outlines the panel of polymorphisms affecting the benefit of aspirin and adenosine diphosphate receptor antagonists, including novel and ongoing studies evaluating whether genotyping may be beneficial in tailoring antiplatelet therapy.

摘要

抗血小板药物如阿司匹林和腺苷二磷酸受体拮抗剂可有效减少复发性缺血事件。这些药物对血小板抑制作用存在明显的个体间差异,这促使人们寻找解释机制和改善治疗方法。近年来,许多遗传多态性与血小板抑制作用降低和抗血小板药物(特别是氯吡格雷和阿司匹林)缺乏临床疗效有关。因此,人们试图根据基因型调整抗血小板治疗,但迄今为止的研究表明,临床获益有限。过去十年中基因组科学的进展和测序技术成本的降低有望实现基因定制的抗血小板治疗。然而,需要更多的证据来阐明哪些多态性可以作为改善治疗的靶点。本综述概述了影响阿司匹林和腺苷二磷酸受体拮抗剂疗效的多态性,包括评估基因分型是否有助于定制抗血小板治疗的新的和正在进行的研究。

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