Medizinische Klinik, Abteilung Kardiologie und Kreislauferkrankungen, University Hospital Tuebingen, Tuebingen, Germany.
J Thromb Haemost. 2010 Jun;8(6):1147-58. doi: 10.1111/j.1538-7836.2010.03791.x. Epub 2010 Feb 1.
Platelet responsiveness to conventional antiplatelet therapy underlies a high interindividual variability influenced by various factors. For instance, antiplatelet therapy does not curtail the expected effects in a relevant number of patients as demonstrated by the occurrence of repeated cardiovascular events including stent thrombosis and/or by inadequate platelet inhibition measured by in vitro platelet function assays. Besides non-genetic factors such as age, gender, liver and renal function and co-medication, considerable variation of antiplatelet drug responsiveness can be attributed to genetic factors including polymorphisms and genetic variants of platelet surface proteins and drug metabolizing enzymes. Nowadays, platelet pharmacogenomics has started a new field with the goal to link genetic information of various drug targets to interindividual variability of drug response. Evolving data from large cohort studies suggest a promising role for pharmacogenomics in the context of antiplatelet therapy. Additionally, with the revolution of low cost and high-throughput genotyping techniques, genetic testing has become affordable for clinical application and individualization of therapy. However, a key issue to define the future role of pharmacogenomics will rely on the benefit and the timeliness of implementing the genetic information into therapeutic decision. Hence, it warrants further investigations to document the prognostic effects of therapeutic alterations in distinct genotypes. Concerning the safety profile of emerging antiplatelet and antithrombotic drugs in certain risk groups it would be fatal to individualize treatment barely on behalf of an atherothrombotic genotype. In contrast, individual risk assessment combining non-genetic information and pharmacogenetic analysis represents a reasonable concept. Here, we provide a review on current data describing the role of pharmacogenomics in the field of antiplatelet drug treatment in cardiovascular patients with future directions.
血小板对常规抗血小板治疗的反应性存在高度个体间变异性，受多种因素影响。例如，抗血小板治疗并没有像预期的那样在许多患者中发挥作用，这表现在反复发生心血管事件（包括支架血栓形成和/或通过体外血小板功能测定）和/或血小板抑制不足。除了年龄、性别、肝肾功能和合并用药等非遗传因素外，抗血小板药物反应性的显著差异可归因于遗传因素，包括血小板表面蛋白和药物代谢酶的多态性和遗传变异。如今，血小板药物基因组学开辟了一个新领域，旨在将各种药物靶点的遗传信息与药物反应的个体间变异性联系起来。来自大型队列研究的不断发展的数据表明，药物基因组学在抗血小板治疗中具有广阔的应用前景。此外，随着低成本、高通量基因分型技术的发展，基因检测已变得可负担得起，并可用于临床应用和治疗的个体化。然而，定义药物基因组学未来作用的关键问题将取决于将遗传信息纳入治疗决策的获益和及时性。因此，有必要进一步研究，以记录不同基因型治疗改变的预后效果。在某些风险群体中，新兴抗血小板和抗血栓形成药物的安全性特征表明，仅仅根据动脉粥样硬化基因型来个体化治疗是致命的。相比之下，结合非遗传信息和药物基因组学分析的个体风险评估代表了一个合理的概念。在这里，我们提供了一篇综述，描述了药物基因组学在心血管病患者抗血小板药物治疗领域中的作用和未来方向。
