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

描述（由申请人提供）

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.