title: Nrf2-related gene expression and exposure to traffic-related air pollution in elderly subjects with cardiovascular disease: An exploratory panel study.
abstract: Gene expression changes are linked to air pollutant exposures in in vitro and animal experiments. However, limited data are available on how these outcomes relate to ambient air pollutant exposures in humans. We performed an exploratory analysis testing whether gene expression levels were associated with air pollution exposures in a Los Angeles area cohort of elderly subjects with coronary artery disease. Candidate genes (35) were selected from published studies of gene expression-pollutant associations. Expression levels were measured weekly in 43 subjects (≤ 12 weeks) using quantitative PCR. Exposures included gaseous pollutants O3, nitrogen oxides (NOx), and CO; particulate matter (PM) pollutants elemental and black carbon (EC, BC); and size-fractionated PM mass. We measured organic compounds from PM filter extracts, including polycyclic aromatic hydrocarbons (PAHs), and determined the in vitro oxidative potential of particle extracts. Associations between exposures and gene expression levels were analyzed using mixed-effects regression models. We found positive associations of traffic-related pollutants (EC, BC, primary organic carbon, PM 0.25-2.5 PAH and/or PM 0.25 PAH, and NOx) with NFE2L2, Nrf2-mediated genes (HMOX1, NQO1, and SOD2), CYP1B1, IL1B, and SELP. Findings suggest that NFE2L2 gene expression links associations of traffic-related air pollution with phase I and II enzyme genes at the promoter transcription level.
authors.affiliation: Occupational and Environmental Medicine Division, Department of Medicine, School of Medicine, University of California, Irvine (UCI), Irvine, California, USA.
authors.forename: Sharine
authors.initials: S
authors.lastname: Wittkopp
authors.affiliation: Department of Epidemiology, School of Medicine, UCI, Irvine, California, USA.
authors.forename: Norbert
authors.initials: N
authors.lastname: Staimer
authors.affiliation: Department of Epidemiology, School of Medicine, UCI, Irvine, California, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tjoa
authors.affiliation: Intrexon Corp., Blacksburg, Virginia, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Stinchcombe
authors.affiliation: Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Daher
authors.affiliation: University of Wisconsin-Madison, Environmental Chemistry and Technology Program, Madison, Wisconsin, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Schauer
authors.affiliation: University of Wisconsin-Madison, Environmental Chemistry and Technology Program, Madison, Wisconsin, USA.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Shafer
authors.affiliation: Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.affiliation: Department of Statistics, School of Information and Computer Sciences, UCI, Irvine, California, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Gillen
authors.affiliation: Department of Epidemiology, School of Medicine, UCI, Irvine, California, USA.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Delfino
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000393:Air Pollutants / Q000009:adverse effects* / Q000032:analysis; D000397:Air Pollution / Q000009:adverse effects* / Q000032:analysis; D002318:Cardiovascular Diseases; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D004784:Environmental Monitoring; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers / Q000187:drug effects*; D006801:Humans; D015141:Los Angeles; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D019007:P-Selectin / Q000235:genetics; D052638:Particulate Matter; D016133:Polymerase Chain Reaction; D012044:Regression Analysis; D053260:Soot / Q000009:adverse effects / Q000032:analysis; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D005819:Genetic Markers; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D019007:P-Selectin; D052638:Particulate Matter; C546937:SELP protein, human; D053260:Soot; D001335:Vehicle Emissions; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1