ARB Research Seminar
This page updated April 1, 2014
Peripheral Blood Gene Expression in Subjects with Coronary Artery Disease and Exposure to Particulate Air Pollutant Components and Size Fractions
Ralph J. Delfino, M.D., Ph.D., University of California, Irvine
April 17, 2014
Cal EPA Headquarters, 1001 "I" Street, Sacramento, CA
Cardiovascular disease outcomes have been associated with exposure to ambient particulate matter (PM) air pollution in many epidemiological studies. Experimental studies have revealed changes in the expression of key genes with exposure to air pollution from fossil fuel combustion. We hypothesized that blood cell gene expression levels along biological pathways relevant to cardiovascular outcomes would be associated with traffic-related air pollutant exposures in elderly subjects with coronary artery disease living in the Los Angeles Air basin.
In the present study data were collected in a cohort panel study funded by National Institute of Health (NIH), National Institute of Environmental Health Sciences (NIEHS). Gene expression data were available for 43 subjects with up to 12 weekly repeated measurements. Candidate genes were selected a priori based on biological function and reported pollutant exposure effects. Exposure measurements were conducted in the indoor and outdoor environment of the subjects' retirement communities and included daily size-fractionated PM mass and PM organic chemical composition, including polycyclic aromatic hydrocarbons (PAH), criteria pollutant gases, total particle number concentration, PM2.5 organic carbon (OC), and PM2.5 markers of primary combustion products. The present ARB-funded study provided accumulation mode PM data for: 1) chemical composition; 2) in vitro generation of reactive oxygen species (ROS) by alveolar macrophages that were exposed to extracts of the weekly PM samples; and 3) source apportionment work. Within-subject relations between air pollutant exposures and normalized gene expression levels were analyzed using adjusted mixed-effects regression models.
Source apportionment results showed that although people spend most of their time indoors, a sizeable portion of indoor PM2.5 particles originate from outdoor mobile sources. Results of regression models for 30 genes showed that traffic-related air pollutants were associated with the expression of 7 genes in important pathways including Nrf2-mediated oxidative stress response, xenobiotic response, inflammation, and platelet activation. PAH and/or ROS from quasi-ultrafine PM (<0.25 micrometers) generally showed stronger associations with gene expression than did accumulation mode PM (0.25-2.5 micrometers). In secondary analyses we found some evidence of effect modification of associations by polymorphisms in selected candidate genes.
Overall, the results obtained in this study support our hypothesis that traffic-related air pollutant exposures affect the expression of genes in pathways that are important to adverse cardiovascular outcomes.
Ralph J. Delfino, M.D., Ph.D., is Professor and Vice Chair for Research and Graduate Studies, Department of Epidemiology, University of California, Irvine, and is Associate Director of the Genetic Epidemiology Research Institute, UC Irvine.
Dr. Delfino's research and teaching focus over the past 30 years has been in environmental epidemiology. His studies have been designed to evaluate the relation of health outcomes to well-characterized air pollution exposures in potentially susceptible populations. His research group has evaluated multiple clinical, biological and genetic factors to understand the effects of air pollutants on respiratory and cardiovascular health. Dr. Delfino's current research is exploring the effects of air pollutant exposures on gene expression changes in several key biological pathways.
Professor Delfino is also evaluating whether genetic variations in candidate genes involved in oxidative stress and other responses modify associations between air pollutants and health outcomes. Dr. Delfino's major ongoing research efforts are to better characterize the pollutant chemicals and particle oxidative potential that are responsible for exposure-response relationships, and to evaluate the health effects of combustion-generated nanoparticles from traffic sources, as compared with larger particles that dominate US EPA-regulated ambient particle mass. Overall, Dr. Delfino's findings are generating new data on susceptibility to the adverse effects of air pollutants and on the role that toxic pollutants in urban air play in respiratory and cardiovascular health.
Professor Delfino received his M.D. degree from the University of Chicago in 1987, and his Ph.D. in epidemiology from McGill University, Montreal in 1993.