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Air quality by genomics interactions in a cardiovascular disease cohort

Principal Investigator: 
,

Duke University

This study will be examining the effect of exposure to air pollution on biomarkers of cardiovascular metabolic risk and blood-borne whole genome gene expression profiles in a cohort with clinically evident heart disease.

Funded under
Status: 
In review
Abstract

Abstract for the 2017 HEI Annual Conference

Gene–Environment Interactions in a Cardiovascular Disease Cohort
Akihiko Nichimura1, Laura McGuinn2, Cavin Ward-Caviness2, Robert B. Devlin2, Lucas M. Neas2, David Diaz-Sanchez2, Wayne E. Cascio2, Petros Koutrakis4, Elizabeth R. Hauser1, William E. Kraus1
1Duke University, Durham, NC; 2US EPA, Chapel Hill, NC; 4Harvard University, Boston, MA.
 
Background We are investigating the effects of acute and chronic air pollution exposure on cardiovascular disease using the 9323-member Duke CATHGEN cohort of individuals undergoing coronary artery catheterization (collected 2001-2011) — CATHGEN includes individuals with and without coronary atherosclerosis. We are addressing three specific aims driven by three hypotheses: 1) Air quality, including PM2.5  and ozone, are related to prevalence of chronic cardiovascular disease and acute cardiovascular events; 2) Specific genetic variants mediate the interaction of air quality and cardiovascular disease and incident events; 3) The interaction of genetic variants and air quality on cardiovascular disease and incidence events are mediated by air quality-induced modifications of the epigenome, peripheral blood gene expression, and circulating metabolic intermediates.
 
For Aim 1 We used a cohort of 5,679 patients undergoing cardiac catheterization between 2002-2009 and residing in NC. Daily PM2.5 concentrations were based on satellite derived Aerosol Optical Depth (AOD) measurements and PM2.5 concentrations from ground monitors; spatially resolved with a 10 x 10 km resolution; matched to each patient’s residential address; and averaged for the year prior to catheterization. The Coronary Artery Disease (CAD) index was used for CAD severity; scores >23 represent a hemodynamically significant coronary artery lesion in at least one major coronary vessel. Logistic regression modeled odds of having CAD or an MI with each 1 μg/m3 increase in annual average PM2.5, adjusting for sex, race, smoking status and socioeconomic status. In adjusted models, a 1 μg/m3 increase in annual average PM2.5 was associated with an 11.1% relative increase in the odds of significant CAD (95% CI: 4.0%-18.6%) and a 14.2% increase in the odds of having a myocardial infarction (MI) within the year prior (95% CI: 3.7% - 25.8%).  Thus, satellite-based estimates of long-term PM2.5 exposure were associated with both coronary artery disease (CAD) and incidence of myocardial infarction (MI) in a cohort of cardiac catheterization patients.
 
For Aim 2 We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis.  Using race-stratified cohorts of 538 African-Americans (AA) and 1562 European-Americans (EA) from a CATHGEN, we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes.  None of the three suggestive interactions in the EA GWIS were replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation.  Thus, we uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution; these genes call out inflammatory pathways perhaps modifying the effects of air pollution on cardiovascular disease risk.
 
This abstract does not necessarily represent EPA policy.
 
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