Browsing by Author "Dowdy, Elaine"

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    Associations Between Residential Proximity to Traffic and Vascular Disease in a Cardiac Catheterization Cohort
    (American Heart Association, Inc, 2018) Ward-Caviness, Cavin K.; Kraus, William E.; Blach, Colette; Haynes, Carol S.; Dowdy, Elaine; Miranda, Marie Lynn; Devlin, Robert; Diaz-Sanchez, David; Cascio, Wayne E.; Mukerjee, Shaibal; Stallings, Casson; Smith, Luther A.; Gregory, Simon G.; Shah, Svati H.; Neas, Lucas M.; Hauser, Elizabeth R.
    Objective—Exposure to mobile source emissions is nearly ubiquitous in developed nations and is associated with multiple adverse health outcomes. There is an ongoing need to understand the specificity of traffic exposure associations with vascular outcomes, particularly in individuals with cardiovascular disease. Approach and Results—We performed a cross-sectional study using 2124 individuals residing in North Carolina, United States, who received a cardiac catheterization at the Duke University Medical Center. Traffic-related exposure was assessed via 2 metrics: (1) the distance between the primary residence and the nearest major roadway; and (2) location of the primary residence in regions defined based on local traffic patterns. We examined 4 cardiovascular disease outcomes: hypertension, peripheral arterial disease, the number of diseased coronary vessels, and recent myocardial infarction. Statistical models were adjusted for race, sex, smoking, type 2 diabetes mellitus, body mass index, hyperlipidemia, and home value. Results are expressed in terms of the odds ratio (OR). A 23% decrease in residential distance to major roadways was associated with higher prevalence of peripheral arterial disease (OR=1.29; 95% confidence interval, 1.08–1.55) and hypertension (OR=1.15; 95% confidence interval, 1.01–1.31). Associations with peripheral arterial disease were strongest in men (OR=1.42; 95% confidence interval, 1.17–1.74) while associations with hypertension were strongest in women (OR=1.21; 95% confidence interval, 0.99–1.49). Neither myocardial infarction nor the number of diseased coronary vessels were associated with traffic exposure. Conclusions—Traffic-related exposure is associated with peripheral arterial disease and hypertension while no associations are observed for 2 coronary-specific vascular outcomes.
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    Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease
    (Public Library of Science, 2016) Ward-Caviness, Cavin K.; Neas, Lucas M.; Blach, Colette; Haynes, Carol S.; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Elaine; Devlin, Robert B.; Diaz-Sanchez, David; Cascio, Wayne E.; Miranda, Marie Lynn; Gregory, Simon G.; Shah, Svati H.; Kraus, William E.; Hauser, Elizabeth R.; National Center for Geospatial Medicine
    There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic (“traffic exposure”)—a recognized vascular disease risk factor—on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3’ untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family, associated with PAD via an interaction with traffic air pollution exposure. These results also highlight the potential for interactions studies, particularly at the genome scale, to reveal novel biology linking environmental exposures to clinical outcomes.