Original Article

Journal of Exposure Science and Environmental Epidemiology (2016) 26, 141–149; doi:10.1038/jes.2014.84; published online 7 January 2015

Nrf2-related gene expression and exposure to traffic-related air pollution in elderly subjects with cardiovascular disease: An exploratory panel study

Sharine Wittkopp1, Norbert Staimer2, Thomas Tjoa2, Timothy Stinchcombe3, Nancy Daher4, James J Schauer5, Martin M Shafer5, Constantinos Sioutas4, Daniel L Gillen6 and Ralph J Delfino2

  1. 1Occupational and Environmental Medicine Division, Department of Medicine, School of Medicine, University of California, Irvine (UCI), Irvine, California, USA
  2. 2Department of Epidemiology, School of Medicine, UCI, Irvine, California, USA
  3. 3Intrexon Corp., Blacksburg, Virginia, USA
  4. 4Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA
  5. 5University of Wisconsin-Madison, Environmental Chemistry and Technology Program, Madison, Wisconsin, USA
  6. 6Department of Statistics, School of Information and Computer Sciences, UCI, Irvine, California, USA

Correspondence: Dr. Ralph J. Delfino, Department of Epidemiology, School of Medicine, University of California, Irvine, 224 Irvine Hall, Irvine, CA 92617-7555, USA. Tel: +1 949 824 1767. Fax: +1 949 824 1343. E-mail: rdelfino@uci.edu

Received 22 February 2014; Revised 8 October 2014; Accepted 14 October 2014
Advance online publication 7 January 2015



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, PM0.25-2.5 PAH and/or PM0.25 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.


longitudinal studies; oxidative stress; transcription; biochemical pathways; particulate matter; air pollution