Platelet Functional Genomics in Cardiovascular Disease

描述(由申请人提供)： 我们推测，血小板粘附性糖蛋白的遗传变异 确定血小板的反应性，从而确定急性缺血冠状动脉的风险 综合症。我们项目的长期目标是验证我们的假设 通过测量患者的血小板功能并进行血小板基因分型 患有急性冠脉综合征的患者。这个项目的一个具体目标 包括确定是否可以将血小板聚集作为衡量 缺血性心脏病患者的血小板功能亢进。肾上腺素 阈值聚集和使用抗受体的全血流式细胞术 诱导结合部位在呈现时和以3个月的间隔结合是两个 用于确定这一特定目标的方法。第二个具体目标 包括在患者组中进行血小板基因分型并比较 将这些频率分配给住院患者的对照组。三分之一 具体目的包括将指标事件与血小板功能和 血小板糖蛋白基因多态性。最后，确定是否 血小板功能和/或血小板糖蛋白基因可以用来预测 后续事件将通过统计分析确定。后续行动： 患者在出现症状后的三个月间隔内进行评估 与急性事件表现相比，血小板功能的差异。如果 基因多态与急性冠脉病变的相关性 症状，然后对几个人进行筛查和干预，如 戒烟、积极的血脂管理和其他预防性医疗 可以为风险最高的患者制定治疗方案。这个 从这个项目中收集的信息也可以为 治疗急性冠脉病变的新药设计 综合症。候选人--S的职业目标包括精炼基本 与各种血小板分析有关的实验室技能，开发一种 更好地了解血小板生理学，最终建立一个 独立的血小板实验室，提升到临床水平 血小板生理学领域的领先者，因为它适用于急性冠状动脉 综合症。通过遵循这些职业目标，候选人最终将成为 能够提出适用于急性冠脉综合征的相关问题 并成为一名独立的临床研究人员。

DESCRIPTION (provided by applicant): We hypothesize that inherited variations of platelet adhesive glycoproteins determine platelet reactivity and hence, risk for acute ischemic coronary syndrome. The long-term objective of our project is to validate our hypothesis by measuring platelet function and performing platelet genotyping in patients who present with the acute coronary syndrome. One specific aim of this project involves determining whether platelet aggregation may be used as a measure of platelet hyperfunction in patients with ischemic heart disease. Epinephrine threshold aggregation and whole blood flow cytometry using anti-receptor induced binding site binding on presentation and at a 3-month interval are two methods utilized to determine this specific aim. A second specific aim involves performing platelet genotyping in the patient group and comparing these frequencies to a control group of hospitalized patients. A third specific aim involves correlating index events with platelet function and platelet glycoprotein polymorphism. Finally a determination of whether platelet function and/or platelet glycoprotein genotype can be used to predict subsequent events will be determined by statistical analysis. Follow-up of patients after a three-month interval from presentation is done to assess any difference in platelet function when compared to acute event presentation. If a correlation exists between genetic polymorphisms and the acute coronary syndrome, then several people can be screened and interventions such as smoking cessation, aggressive lipid management and other preventive medical therapies may be instituted for patients who are at greatest risk. The information gleaned from this project can also lead to new ideas for the design of newer medications used for the therapy of the acute coronary syndrome. The candidate?s career goal includes the refinement of basic laboratory skills pertaining to various platelet assays, development of a better understanding of platelet physiology, eventual establishment of an independent platelet laboratory, and advancement to the level of clinical leader in the field of platelet physiology as it applies to the acute coronary syndrome. By following these career goals, the candidate will eventually be able to ask pertinent questions applicable to the acute coronary syndrome and platelet function and become an independent clinical investigator.