Original Article

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

  • Journal of Exposure Science and Environmental Epidemiology (2016) 26, 141149 (2016)
  • doi:10.1038/jes.2014.84
  • Download Citation
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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, 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.

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Acknowledgements

This work was supported by the National Institute of Environmental Health Sciences at the National Institutes of Health (NIH, R01-ES12243 and R21-ES016420), the California Air Resources Board (contracts 03-329 and 09-341), and the National Center for Research Resources at the National Institutes of Health (NIH, MO1-RR00827). SW is supported by the National Institute of Environmental Health Sciences at the National Institutes of Health (NIH, F30 ES21107) and the Stanley Behrens UCI Graduate Division Public Impact Fellowship. ND is supported by the University of Southern California Provost's PhD fellowship. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies. We thank the Department of Epidemiology and General Clinical Research Center, University of California Irvine; Department of Civil and Environmental Engineering, University of Southern California (USC); the Wisconsin State Laboratory of Hygiene; the California Air Resources Board; and the South Coast Air Quality Management District.

Author information

Affiliations

  1. Occupational and Environmental Medicine Division, Department of Medicine, School of Medicine, University of California, Irvine (UCI), Irvine, California, USA

    • Sharine Wittkopp
  2. Department of Epidemiology, School of Medicine, UCI, Irvine, California, USA

    • Norbert Staimer
    • , Thomas Tjoa
    •  & Ralph J Delfino
  3. Intrexon Corp., Blacksburg, Virginia, USA

    • Timothy Stinchcombe
  4. Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA

    • Nancy Daher
    •  & Constantinos Sioutas
  5. University of Wisconsin-Madison, Environmental Chemistry and Technology Program, Madison, Wisconsin, USA

    • James J Schauer
    •  & Martin M Shafer
  6. Department of Statistics, School of Information and Computer Sciences, UCI, Irvine, California, USA

    • Daniel L Gillen

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Competing interests

CS receives royalties from SKC for the air sampling device (Sioutas Personal Cascade Impactor Sampler) used in this research.

Corresponding author

Correspondence to Ralph J Delfino.

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    Supplementary Material

Supplementary Information accompanies the paper on the Journal of Exposure Science and Environmental Epidemiology website (http://www.nature.com/jes)