Exposure to NO2, CO, and PM2.5 Is Linked to Regional DNA Methylation Differences in Asthma

Details

• Personal Author:
  Balmes JR ; de Planell-Saguer M ; Dinakarpandian D ; Hammond SK ; Lucas RW ; Miller RL ; Nadeau KC ; Paglino T ; Prunicki M ; Sabatti C ; Stell L ; Zhou X
• Description:
  Background: DNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation (Foxp3 and IL10) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites. We recruited subjects from Fresno, California, an area known for high levels of AAPs. Blood samples and responses to questionnaires were obtained (n = 188), and in a subset of subjects (n = 33), repeat samples were collected 2 years later. Average measures of AAPs were obtained for 1, 15, 30, 90, 180, and 365 days prior to each blood draw to estimate the short-term vs. long-term effects of the AAP exposures. Results: Asthma was significantly associated with higher differentially methylated regions (DMRs) of the Foxp3 promoter region (p = 0.030) and the IL10 intronic region (p = 0.026). Additionally, at the 90-day time period (90 days prior to the blood draw), Foxp3 methylation was positively associated with NO2, CO, and PM2.5 exposures (p = 0.001, p = 0.001, and p = 0.012, respectively). In the subset of subjects retested 2 years later (n = 33), a positive association between AAP exposure and methylation was sustained. There was also a negative correlation between the average Foxp3 methylation of the promoter region and activated Treg levels (p = 0.039) and a positive correlation between the average IL10 methylation of region 3 of intron 4 and IL10 cytokine expression (p = 0.030). Conclusions: Short-term and long-term exposures to high levels of CO, NO2, and PM2.5 were associated with alterations in differentially methylated regions of Foxp3. IL10 methylation showed a similar trend. For any given individual, these changes tend to be sustained over time. In addition, asthma was associated with higher differentially methylated regions of Foxp3 and IL10. [Description provided by NIOSH]
• Subjects:
  Air Pollution Asthma Asthma, Occupational Carbon Monoxide Immune System Nitrogen Dioxide Occupational Health Pathology Safety
• Keywords:
  Air Pollution Author Keywords: Ambient Air Pollution Carbon Monoxide Children Cytokines DNA Damage Epigenetics Immune Reaction Immune System Nitrogen Dioxide Oxidative Stress Regulatory T Cell

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• ISSN:
  1868-7083
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Arizona ; California ; New York ; OSHA Region 2 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  2
• Volume:
  10
• NIOSHTIC Number:
  nn:20056675
• Citation:
  Clin Epigenetics 2018 Jan; 10:2
• Contact Point Address:
  Kari C. Nadeau, Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, CA 94305, USA
• Email:
  knadeau@stanford.edu
• CAS Registry Number:
  Carbon monoxide (CAS RN 630-08-0) ; Nitrogen dioxide (CAS RN 10102-44-0)
• Federal Fiscal Year:
  2018
• Performing Organization:
  University of California, Berkeley
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Clinical Epigenetics
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8757e1390d8d86d8d734bafb4cca9428d7b4c964b8faaa1a8805a1657c26eaad9397829996355b3d29dc4ca6a59b72e9b3f6fd7740ad314a9e362afb4137e1b5
• Download URL:
  https://stacks.cdc.gov/view/cdc/214230/cdc_214230_DS1.pdf
• File Type:
  [PDF - 979.01 KB ]