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

描述(由申请人提供) 这项研究将描述与交通相关的空气污染暴露与心脏结构和功能的关系，并确定改变空气污染和心脏结构和功能改变关系的新的遗传因素。 背景：与交通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也不明确。在动脉粥样硬化的多种族研究(MESA)中，居住在主要道路附近(暴露于与交通相关的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，LVM是包括心力衰竭在内的心血管疾病结局的重要中介。在我们在MESA进行的一项有限的候选基因研究中，几个与炎症、血管激活、凝血和血压有关的基因(ALOX15、AGTR1、SCNN1A和VWF)似乎改变了主干道与LVM之间的关联，提示了重要的机制。使用更先进的暴露指标(查看特定污染物及其与心脏结构和功能的关系)，在另一个队列中重复，并扩大这项工作的范围，以更好地了解这种关系中哪些新的遗传因素是重要的，将提高对空气污染影响心脏疾病的机制的理解，并提出治疗干预措施。 目的：具体目标1：在两个队列(MESA和心血管健康研究，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2：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中选择候选对象和先验结果)，最终目标是了解机制。 方法：本研究将使用线性回归来检验为本研究开发的与交通相关的空气污染暴露测量与心脏结构和功能测量之间的关系。然后将使用线性回归，特别是检查空气污染暴露与MESA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。最后，研究人员将在CHS中复制MESA的发现。

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.