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Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: a panel study in four European countries

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Title: Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: a panel study in four European countries
Authors: Mostafavi, N
Vermeulen, R
Ghantous, A
Hoek, G
Probst-Hensch, N
Herceg, Z
Tarallo, S
Naccarati, A
Kleinjans, JCS
Imboden, M
Jeong, A
Morley, D
Amaral, AFS
Van Nunen, E
Gulliver, J
Chadeau, M
Vineis, P
Vlaanderen, J
Item Type: Journal Article
Abstract: Background One of the potential mechanisms linking air pollution to health effects is through changes in DNA-methylation, which so far has mainly been analyzed globally or at candidate sites. Objective We investigated the association of personal and ambient air pollution exposure measures with genome-wide DNA-methylation changes. Methods We collected repeated 24-hour personal and ambient exposure measurements of particulate matter (PM2.5), PM2.5 absorbance, and ultrafine particles (UFP) and peripheral blood samples from a panel of 157 healthy non-smoking adults living in four European countries. We applied univariate mixed-effects models to investigate the association between air pollution and genome-wide DNA-methylation perturbations at single CpG (cytosine-guanine dinucleotide) sites and in Differentially Methylated Regions (DMRs). Subsequently, we explored the association of air pollution-induced methylation alterations with gene expression and serum immune marker levels measured in the same subjects. Results Personal exposure to PM2.5 was associated with methylation changes at 13 CpG sites and 69 DMRs. Two of the 13 identified CpG sites (mapped to genes KNDC1 and FAM50B) were located within these DMRs. In addition, 42 DMRs were associated with personal PM2.5 absorbance exposure, 16 DMRs with personal exposure to UFP, 4 DMRs with ambient exposure to PM2.5, 16 DMRs with ambient PM2.5 absorbance exposure, and 15 DMRs with ambient UFP exposure. Correlation between methylation levels at identified CpG sites and gene expression and immune markers was generally moderate. Conclusion This study provides evidence for an association between 24-hour exposure to air pollution and DNA-methylation at single sites and regional clusters of CpGs. Analysis of differentially methylated regions provides a promising avenue to further explore the subtle impact of environmental exposures on DNA-methylation.
Issue Date: 24-Jul-2018
Date of Acceptance: 17-Jul-2018
URI: http://hdl.handle.net/10044/1/62313
DOI: https://dx.doi.org/10.1016/j.envint.2018.07.026
ISSN: 0160-4120
Publisher: Elsevier
Start Page: 11
End Page: 21
Journal / Book Title: Environment International
Volume: 120
Copyright Statement: © 2018 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 308610
Keywords: Air pollution
DNA-methylation
Fine particles
Immune markers
Ultrafine particles
MD Multidisciplinary
Environmental Sciences
Publication Status: Published
Online Publication Date: 2018-07-25
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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