Studies on genetic testing for the possible diagnosis of aspirin resistance

最近的研究表明，对阿司匹林和其他抗血小板药物的耐药性是一种公认的状态。那些对阿司匹林治疗有抗药性的人更容易复发血栓形成。因此，研究发现阿司匹林抵抗的基因对预防动脉粥样硬化血栓形成事件是极其重要的，动脉粥样硬化血栓形成事件是这个国家的主要死亡原因。本研究的目的是分析阿司匹林抵抗与血栓形成和止血相关基因变异的关系，为血栓形成的个体化治疗提供基础数据。我们首先建立了最佳的实验条件，在体外评估阿司匹林抵抗，使用血小板功能分析仪，PFA 100。在大多数情况下，向正常富血小板血浆中加入高浓度阿司匹林延长了闭塞时间。然而，添加低浓度的阿司匹林也会这样做，但大约30%的正常个体对阿司匹林没有反应（即，在临界值范围内）。对阿司匹林“耐药”的人的特征是具有高基础血小板反应性，通过其他血小板功能测试评估的高血小板功能（在全血聚集仪WBA-Neo和使用富血小板血浆的传统光学聚集仪中的胶原蛋白刺激的血小板功能）。我们发现了几种可能与阿司匹林抵抗相关的遗传多态性。我们的研究结果提示处方前评估抗血小板治疗的疗效。前瞻性研究是必要的，以建立遗传多态性和抗血小板治疗的结果之间的关系和因果关系。

Recent studies have revealed that resistance to aspirin and other antiplatelet drugs is a commonly recognized status. Those on aspirin therapy who are resistant to this drug are more prone to the recurrence of thrombosis. Thus, research to find genes responsible for aspirin resistance is extremely important to prevent atherothrombotic events, which are the leading cause of death in this country. The purpose of this study was to analyze the mechanisms of aspirin resistance in relationship with the variability in genes responsible for thrombosis and hemostasis, and to obtain basic data for individualized treatment of thrombosis. We first established the optimal experimental conditions for the in vitro assessment of aspirin resistance, using a platelet function analyzer, PFA100. Addition of aspirin at high concentration to normal platelet-rich plasma prolonged the occlusion time over the cut-off range in most cases. Addition of low concentration of aspirin, however, also did so but 〜30% of normal individuals failed to respond to aspirin (i.e., remained within the cut-off range). Those who are "resistant" to aspirin were characteristic as having high basal platelet reactivity, high platelet function as assessed by other platelet function tests (collagen-stimulated platelet function in a whole-blood aggregometer WBA-Neo and conventional optical aggregometer using platelet rich plasma). We found several genetic polymorphisms that are possibly associated with aspirin resistance. Our results are suggestive for the pre-prescription assessment of the efficacies of antiplatelet therapies. Prospective studies are necessary to establish the relationship and causation between genetic polymorphisms and the outcome of antiplatelet therapies.