Genetic Modification of Triggers of Acute Myocardial Infarction

描述（由申请方提供）：大多数关于心血管疾病的流行病学研究都集中在导致数年至数十年后发病的长期暴露上。然而，最近的研究领域集中在触发急性心肌梗死发作的短期事件上。研究表明，剧烈的体力消耗和咖啡摄入是急性心肌梗死的两个诱因。然而，遗传变异可能会改变对重体力劳动和咖啡的急性影响的敏感性。我们将使用病例交叉研究的独特特征来评估遗传变异对咖啡摄入和重体力劳动引发心肌梗死的潜在影响。病例交叉设计是一种研究对急性事件风险的短暂影响的方法。我们不像通常的病例对照设计那样将一些个体与其他个体进行比较，而是在个体内部进行比较，将危险期（事件发生前的时间段）与对照期进行比较。因此，任何固定的（即非随时间变化的）特征，如年龄、性别、遗传背景等，都不能作为主要效应进行评估。然而，固定特性可以作为瞬态暴露的修饰符进行评估。我们的总体目标是通过检测参与交感神经系统、肾素-血管紧张素系统、咖啡因代谢的基因以及介导咖啡因某些生理效应的基因，来确定触发急性心肌梗死的遗传修饰物。我们还将评估在最近的全基因组关联研究中发现的21个多态性。研究人群包括1994年至2004年在哥斯达黎加的中央谷招募的2,300例非致死性心肌梗死病例。DNA已经存在于这个群体中。这项拟议的研究是新颖的，并提供了一个不寻常的机会，以扩大我们对遗传背景如何改变瞬时风险暴露的触发效应的理解。了解心肌梗死触发因素的变异性的遗传基础对于识别可以改变其生活方式以改善健康的易感亚群至关重要。 公共卫生相关性：这项研究将有助于了解心肌梗死触发因素反应变异性的遗传基础。这项研究的结果可能有助于确定可以改变生活方式以改善健康的易感亚群。

DESCRIPTION (provided by applicant): Most epidemiological studies on cardiovascular disease have concentrated on long-term exposures that contribute to the onset of disease years to decades later. A more recent area of research has, however, focused on the short-term events that trigger the onset of an acute myocardial infarction. It has been shown that heavy physical exertion and coffee intake are two triggers of acute myocardial infarction. However, it is possible that genetic variation alter the susceptibility to the acute effects of heavy physical exertion and coffee. We will use the unique characteristics of the case-crossover study to assess potential effect modification by genetic variation on the triggering of myocardial infarction by coffee intake and heavy physical exertion. The case-crossover design is a method for studying transient effects on the risk of acute events. Rather than comparing some individuals with others, as would a usual case-control design, we make comparisons within individuals, comparing the hazard period (time period right before the event) with a control period. Therefore, any fixed (i.e. not time-varying) characteristics like age, sex, genetic background, etc. cannot be assessed as main effects. However, fixed characteristics can be evaluated as modifiers of the transient exposure. Our overall objective is to identify genetic modifiers of triggers of acute myocardial infarction by examining genes involved in the sympathetic nervous system, renin-angiotensin system, caffeine metabolism, and genes that mediate some of the physiologic effects of caffeine. We will also evaluate 21 polymorphisms identified in recent genome-wide association studies. The study population consists of 2,300 incident cases of nonfatal myocardial infarction in the Central Valley of Costa Rica recruited from 1994 to 2004. DNA is already available in this population. The proposed study is novel and offers an unusual opportunity to expand our understanding of how genetic background can modify the triggering effect of transient risk exposures. Understanding the genetic basis for the variability in response to triggers of myocardial infarction is essential for identifying susceptible sub-populations that can modify their life styles to improve health. PUBLIC HEALTH RELEVANCE: This study will help understand the genetic basis for the variability in response to triggers of myocardial infarction. Results from this study may help to identify susceptible sub-populations that can modify their life styles to improve health.