Milanowski Lukasz, Pordzik Justyna, Janicki Piotr K, Postula Marek
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland.
Perioperative Genomics Laboratory, Penn State College of Medicine, Hershey, PA 17033, USA.
Pharmacogenomics. 2016 Jun;17(8):953-71. doi: 10.2217/pgs.16.21. Epub 2016 Jun 7.
Ischemic stroke has been named one of the leading causes of death worldwide. Whereas numerous biological mechanisms and molecules were found to be associated with stroke, platelets are particularly contributive to its pathogenesis. Recent data indicate considerable variability in platelet phenotype which accounts for differences in platelet surface receptor function, count and reactivity. These features collectively influence both the events leading to a disease and effectiveness of antiplatelet therapies. Consequently, genetic variants predisposing to cerebrovascular diseases can be sequenced using a wide array of techniques and become a useful tool in clinical setting. In this review, we provide an outline of common platelet polymorphisms that impose risk on ischemic stroke development and should be evaluated as targets to improve treatment. As study results are often inconsistent, partly due to differences in demographic characteristics between study populations and the fact that the functional impact of these variants has been relatively small, we conclude that both rare, low-frequency and common variants might account for genetic contribution on abnormal platelet response to antiplatelet drugs.
缺血性中风已被列为全球主要死因之一。尽管发现众多生物学机制和分子与中风有关,但血小板对其发病机制的影响尤为显著。最新数据表明,血小板表型存在显著差异,这导致血小板表面受体功能、数量和反应性有所不同。这些特征共同影响导致疾病的事件以及抗血小板治疗的效果。因此,可使用多种技术对易患脑血管疾病的基因变异进行测序,并使其成为临床环境中的有用工具。在本综述中,我们概述了常见的血小板多态性,这些多态性会增加缺血性中风发生的风险,应作为改善治疗的靶点进行评估。由于研究结果往往不一致,部分原因是研究人群的人口统计学特征存在差异,以及这些变异的功能影响相对较小,我们得出结论,罕见、低频和常见变异都可能对血小板对抗血小板药物的异常反应产生遗传影响。