Gene-air pollution interactions and cardiac structure and function in MESA and CH

MESA 和 CH 中基因与空气污染的相互作用以及心脏结构和功能

• 批准号: 8027432
• 负责人: VICTOR C VAN HEE
• 金额: $ 16.18万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-27 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8027432
• 关键词: Gene; air; pollution; interactions; cardiac

DESCRIPTION (provided by applicant) This research will describe the relationship between traffic-related air pollution exposures and cardiac structure & function, and identify novel genetic factors that modify the relationship between air pollution and altered cardiac structure & function. Background: Traffic-related air pollution is associated with cardiovascular disease and congestive heart failure, but the mechanisms responsible for this association are unclear. Additionally, specific pollutants with the greatest impact on cardiac structure and function are poorly defined. In the Multi-Ethnic Study of Atherosclerosis (MESA), residential proximity to major roadways (a relatively crude metric of exposure to traffic-related air pollution) has been demonstrated to be associated with increased left ventricular mass (LVM), an important intermediate for cardiovascular disease outcomes including heart failure. In a limited candidate gene study that we have conducted in MESA, several genes involved in inflammation, vascular activation, coagulation, and blood pressure (ALOX15, AGTR1, SCNN1A, and VWF) appear to modify the association between proximity to major roadways and LVM, suggesting important mechanisms. The use of more advanced exposure metrics (looking at specific pollutants and their relationship to cardiac structure and function), replication in another cohort, and broadening the scope of this work to better understand which novel genetic factors are important in this relationship will improve understanding of the mechanisms by which air pollution affects heart disease and suggest therapeutic interventions. Aims: Specific Aim 1: Establish the relationship between traffic-related air pollution exposures and cardiac structure & function using advanced exposure metrics in two cohorts (MESA and the Cardiovascular Health Study, or CHS). Specific Aim 2: Determine the genetic factors (selecting candidates from ongoing genome- wide association studies and a priori) that modify the relationship between air pollution exposure and cardiac structure and function, with an ultimate goal of understanding mechanisms. Methods: This study will use linear regression to examine the relationship between traffic-related air pollution exposure measurements developed for this study and measures of cardiac structure and function. Linear regression, specifically examining the interaction of air pollution exposures with candidate genes in MESA, will then be used, selecting candidate loci from prior genome-wide association studies. Finally, the investigators will replicate MESA findings in CHS.

描述（由申请人提供） 这项研究将描述交通相关的空气污染暴露与心脏结构和功能之间的关系，并确定改变空气污染与心脏结构和功能改变之间关系的新遗传因素。 背景资料：与心脏病相关的空气污染与心血管疾病和充血性心力衰竭有关，但这种联系的机制尚不清楚。此外，对心脏结构和功能影响最大的特定污染物的定义很差。在动脉粥样硬化的多种族研究（梅萨）中，住宅靠近主要道路（暴露于交通相关空气污染的相对粗略的指标）已被证明与左心室质量（LVM）增加有关，这是心血管疾病结局（包括心力衰竭）的重要中间体。 在我们在梅萨进行的有限候选基因研究中，涉及炎症、血管激活、凝血和血压的几个基因（ALOX 15、AGTR 1、SCNN1A和VWF）似乎改变了靠近主要道路和左心室质量之间的关联，这表明了重要的机制。使用更先进的暴露指标（研究特定污染物及其与心脏结构和功能的关系），在另一个队列中复制，并扩大这项工作的范围，以更好地了解哪些新的遗传因素在这种关系中很重要，这将提高对空气污染影响心脏病的机制的理解，并提出治疗干预措施。 目的：具体目标1：在两个队列（梅萨和心血管健康研究或CHS）中使用先进的暴露指标建立交通相关空气污染暴露与心脏结构和功能之间的关系。 具体目标二：确定改变空气污染暴露与心脏结构和功能之间关系的遗传因素（从正在进行的全基因组关联研究和先验中选择候选者），最终目标是了解机制。 研究方法：本研究将使用线性回归来检查本研究开发的交通相关空气污染暴露测量值与心脏结构和功能测量值之间的关系。然后将使用线性回归，特别是检查空气污染暴露与梅萨中候选基因的相互作用，从先前的全基因组关联研究中选择候选基因座。最后，研究人员将在CHS中复制梅萨结果。