Genetic Predictors of QT Response During Exercise

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。 这个K23建议的总体目标是建立在我以前在这方面的经验，以确定遗传和 运动应激反应的其他预测因子，从而开始建立一个新的框架， 心律失常导致猝死的风险。具体目标将确定所定义的 以及调节中间电生理表型变异性的新多态性，包括 运动应激和固有心率的反应。在具体目标1中，我将表现为QT和RR 在正常受试者的运动和恢复过程中的反应，并测试遗传多态性的作用， 介导这些反应的可变性。在具体目标2中，我将表型内在QT和RR反应 在正常受试者的运动和恢复过程中，并测试遗传多态性在介导 这些反应的变化。在具体目标3中，1将确定QT延长药物对 固有心率和QT间期。这些资源使我能够进一步发展为临床研究者， 测试这些目标背后的假设已经到位。这个奖项将提高我的技能，作为一个临床 研究者通过临床研究、明确的教育计划和正式的指导过程， 高度支持和富有成效的研究和指导环境。这样一来， 最大限度地提高我的目标，发展成为一个独立的调查员，有一个强大的研究计划， 办妥了一批 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，因此与 公共卫生

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 3,1 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.