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: 7989323
• 负责人: ANA B BAYLIN
• 金额: $ 28.54万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7989323
• 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; 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; 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在几年到几十年后导致疾病发病的长期暴露。然而，最近的一个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，繁重的体力消耗和喝咖啡是急性心肌梗死的两个诱因。然而，基因变异可能会改变人们对剧烈体力消耗和咖啡的敏感度。我们将利用病例交叉研究的独特特点来评估基因变异对咖啡摄入和繁重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急性事件风险的瞬时效应的方法。我们不是像通常的病例对照设计那样将一些个体与另一些个体进行比较，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，任何固定的(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，固定特性可以作为瞬时暴露的修饰符进行评估。我们的总体目标是通过检测与交感神经系统、肾素-血管紧张素系统、咖啡因代谢相关的基因以及咖啡因的某些生理效应的基因，来确定急性心肌梗死的触发因素。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。研究人群包括1994年至2004年在哥斯达黎加中央山谷招募的2300例非致命性心肌梗死病例。DNA已经在这个群体中得到了。这项拟议的研究是新颖的，为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提供了一个不同寻常的机会。了解心肌梗死诱发因素变化的遗传基础，对于识别能够改变其生活方式以改善健康状况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的变异性的遗传基础。这项研究的结果可能有助于识别能够改变他们的生活方式以改善健康的易感亚人群。