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Epigenetics. 2014 Mar;9(3):448-58. doi: 10.4161/epi.27584. Epub 2014 Jan 2.

Air pollution and gene-specific methylation in the Normative Aging Study: association, effect modification, and mediation analysis.

Author information

1
Department of Environmental Health; Harvard School of Public Health; Boston, MA USA; Department of Biostatistics; Harvard School of Public Health; Boston, MA USA.
2
Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
3
Department of Medical Statistics; London School of Hygiene and Tropical Medicine; London, UK.
4
Department of Biostatistics; Harvard School of Public Health; Boston, MA USA.
5
Center of Molecular and Genetic Epidemiology; University of Milan; Milan, Italy.
6
VA Boston Healthcare System and the Department of Medicine; Boston University School of Medicine; Boston, MA USA.

Abstract

The mechanisms by which air pollution has multiple systemic effects in humans are not fully elucidated, but appear to include inflammation and thrombosis. This study examines whether concentrations of ozone and components of fine particle mass are associated with changes in methylation on tissue factor (F3), interferon gamma (IFN-γ), interleukin 6 (IL-6), toll-like receptor 2 (TLR-2), and intercellular adhesion molecule 1 (ICAM-1). We investigated associations between air pollution exposure and gene-specific methylation in 777 elderly men participating in the Normative Aging Study (1999-2009). We repeatedly measured methylation at multiple CpG sites within each gene's promoter region and calculated the mean of the position-specific measurements. We examined intermediate-term associations between primary and secondary air pollutants and mean methylation and methylation at each position with distributed-lag models. Increase in air pollutants concentrations was significantly associated with F3, ICAM-1, and TLR-2 hypomethylation, and IFN-γ and IL-6 hypermethylation. An interquartile range increase in black carbon concentration averaged over the four weeks prior to assessment was associated with a 12% reduction in F3 methylation (95% CI: -17% to -6%). For some genes, the change in methylation was observed only at specific locations within the promoter region. DNA methylation may reflect biological impact of air pollution. We found some significant mediated effects of black carbon on fibrinogen through a decrease in F3 methylation, and of sulfate and ozone on ICAM-1 protein through a decrease in ICAM-1 methylation.

KEYWORDS:

air pollution; effect modification; elderly; gene-specific DNA methylation; mediation analysis; traffic

PMID:
24385016
PMCID:
PMC4053463
DOI:
10.4161/epi.27584
[Indexed for MEDLINE]
Free PMC Article
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