Genetic Modification of Triggers of Acute Myocardial Infarction

急性心肌梗死触发因素的基因改造

• 批准号: 8122216
• 负责人: ANA B BAYLIN
• 金额: $ 15.6万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8122216
• 关键词: Acute; Acute myocardial infarction; Adenosine; Adrenergic Receptor; Age; Angiotensinogen; Area; Arterial Fatty Streak; Caffeine; Cardiovascular Diseases; Catecholamines; Catechols; Cell physiology; Characteristics; Chromogranins; Coffee; Consumption; Costa Rica; Cross-Over Studies; Crossover Design; Cytochrome P-450 CYP1A2; DNA; Data; Deaminase; Dopamine D1 Receptor; Dopamine D2 Receptor; Epidemiologic Studies; Event; Exertion; Exposure to; G protein coupled receptor kinase; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Health; Individual; Intake; Life Style; Mediating; Metabolism; Methods; Methyltransferase; Modification; Morbidity - disease rate; Myocardial Infarction; Onset of illness; Peptidyl-Dipeptidase A; Physiological; Population; Population Study; Predisposition; Receptor Gene; Receptor, Angiotensin, Type 1; Recruitment Activity; Renin-Angiotensin System; Research; Research Design; Research Methodology; Risk; Statistical Methods; Sympathetic Nervous System; Time; Variant; adenosine deaminase; base; case control; design; genome wide association study; hazard; improved; mortality; novel; public health relevance; receptor function; response; sex

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.

描述（由申请人提供）：大多数关于心血管疾病的流行病学研究都集中于导致数年至数十年后疾病发作的长期暴露。然而，最近的研究领域集中于引发急性心肌梗死发作的短期事件。研究表明，剧烈体力消耗和摄入咖啡是急性心肌梗塞的两个诱因。然而，遗传变异可能会改变对剧烈体力消耗和咖啡的急性影响的易感性。我们将利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剧烈体力消耗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瞬时影响的方法。我们不像通常的病例对照设计那样将某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）与控制期进行比较。因此，任何固定（即不随时间变化）的特征，如年龄、性别、遗传背景等都不能被评估为主效应。然而，固定特性可以被评估为瞬态暴露的修饰符。我们的总体目标是通过检查涉及交感神经系统、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急性心肌梗死触发因素的遗传修饰因素。我们还将评估最近全基因组关联研究中发现的 21 种多态性。研究人群由 1994 年至 2004 年在哥斯达黎加中央山谷招募的 2,300 例非致命性心肌梗塞病例组成。该人群的 DNA 已经可用。拟议的研究是新颖的，并提供了一个不寻常的机会来扩大我们对遗传背景如何改变短暂风险暴露的触发效应的理解。了解心肌梗死触发因素反应变异性的遗传基础对于识别易感亚群至关重要，这些亚群可以改变生活方式以改善健康。 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的遗传基础。这项研究的结果可能有助于识别易感人群，他们可以通过改变生活方式来改善健康。