Genetic Predictors of QT Response During Exercise

描述（由申请人提供）： 项目概述：对运动应激的反应是公认的心脏病预后预测因子。本K23建议的总体目标是建立在我以前在这一领域的经验，以确定运动应激反应的遗传和其他预测因子，从而开始开发一个新的框架，以接近心律失常导致猝死的风险。具体目标将确定已定义的和新的多态性在调节中间电生理表型的变异性中的作用，包括对运动应激和固有心率的反应。在具体目标1中，我将对正常受试者在运动和恢复过程中的QT和RR反应进行表型分析，并测试遗传多态性在介导这些反应变异性中的作用。在具体目标2中，我将对正常受试者在运动和恢复过程中的内在QT和RR反应进行表型分析，并测试遗传多态性在介导这些反应变异性中的作用。在具体目标3中，我将确定QT延长药物对固有心率和QT间期的影响。我作为一名临床研究者进一步发展和测试这些目标背后的假设的资源已经到位。该奖项将通过临床研究，明确的教育计划以及在高度支持和富有成效的研究和指导环境中的正式指导过程来提高我作为临床研究者的技能。通过这种方式，最大限度地提高了我作为一名独立调查员的目标，并实现了一个强大的研究计划。 相关性：心脏性猝死每年导致42万美国人死亡。这项研究有可能允许识别有心脏性猝死风险的个体，因此对公共卫生具有重要意义。 (End摘要）

DESCRIPTION (provided by applicant): Project Summary: Response to exercise stress is a well-recognized predictor of outcome in heart disease. The overall goal of this K23 proposal to is build on my previous experience in this area to identify genetic and other predictors of response to exercise stress, and thereby begin to develop a new framework for approaching risk of sudden death due to arrhythmias. The Specific Aims will determine the role of defined and new polymorphisms in modulating variability in intermediate electrophysiologic phenotypes, including responses to exercise stress and intrinsic heart rate. In Specific Aim 1, I will phenotype QT and RR responses during exercise and recovery in normal subjects, and test the role of genetic polymorphisms in mediating variability in these responses. In Specific Aim 2, I will phenotype intrinsic QT and RR response during exercise and recovery in normal subjects, and test the role of genetic polymorphisms in mediating variability in these responses. In Specific Aim 3, I will determine the effect of a QT-prolonging drug on intrinsic heart rate and QT interval. The resources for me to develop further as a clinical investigator and to test the hypotheses underlying these aims are in place. This award will enhance my skills as a clinical investigator through clinical research, a defined educational program, and a formal mentoring process in a highly supportive and productive research and mentoring environment. In this way, the likelihood is maximized that my goal of developing as an independent investigator with a robust research program will be achieved. Relevance: Sudden cardiac death kills 420,000 Americans each year. This research has the potential to permit identification of individuals at risk for sudden cardiac death and therefore has significant relevance to public health. (End of Abstract)