Abstract
Background: DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55). Methods: One-year average ambient fine particulate matter (PM2.5) and oxides of nitrogen (NOX) concentrations were predicted at participants' (n = 1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina's Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution. Results: At a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM2.5 and none were associated with NOX. Cg20455854 had the smallest p-value for the association with PM2.5 (p = 2.77 × 10-5). mRNA expression profiles of genes near three of the PM2.5-associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM2.5 exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure. Conclusions: We observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.
Original language | English (US) |
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Article number | 119 |
Journal | Environmental Health: A Global Access Science Source |
Volume | 15 |
Issue number | 1 |
DOIs | |
State | Published - Jan 12 2016 |
Funding
This work was supported by National Institute of Environmental Health Sciences (NIEHS, 1 F31 ES025475-01, P30 ES007033, P50 ES015915-01). This research was also supported by contracts T32 HL007902, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, and 2R01 HL071759 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-TR-001079 from NCRR. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This publication was developed under a STAR research assistance agreement, No. RD831697 (MESA Air), awarded by the U.S Environmental protection Agency. It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication. The MESA Epigenomics & Transcriptomics Study was funded by NHLBI grant 1R01HL101250-01 to Wake Forest University Health Sciences. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI, USEPA, or NIEHS.
Keywords
- ANKHD1
- ANKRD11
- Air pollution
- BAZ2B
- DNA methylation
- LGALS2
- NO
- PM
- PPIE
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Health, Toxicology and Mutagenesis
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Long-term outdoor air pollution and DNA methylation in circulating monocytes: results from the Multi-Ethnic Study of Atherosclerosis (MESA)
Chi, G. C. (Creator), Liu, Y. (Contributor), MacDonald, J. W. (Creator), Barr, R. G. (Contributor), Donohue, K. M. (Creator), Hensley, M. D. (Creator), Hou, L. (Contributor), McCall, C. E. (Creator), Reynolds, L. M. (Creator), Siscovick, D. S. (Creator) & Kaufman, J. D. (Creator), figshare, 2016
DOI: 10.6084/m9.figshare.c.3639035, https://figshare.com/collections/Long-term_outdoor_air_pollution_and_DNA_methylation_in_circulating_monocytes_results_from_the_Multi-Ethnic_Study_of_Atherosclerosis_MESA_/3639035
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