title: Air pollution and gene-specific methylation in the Normative Aging Study: association, effect modification, and mediation analysis.
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.
authors.affiliation: Department of Environmental Health; Harvard School of Public Health; Boston, MA USA; Department of Biostatistics; Harvard School of Public Health; Boston, MA USA.
authors.forename: Marie-Abele
authors.initials: MA
authors.lastname: Bind
authors.affiliation: Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lepeule
authors.affiliation: Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Zanobetti
authors.affiliation: Department of Medical Statistics; London School of Hygiene and Tropical Medicine; London, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasparrini
authors.affiliation: Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.affiliation: Department of Biostatistics; Harvard School of Public Health; Boston, MA USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: Center of Molecular and Genetic Epidemiology; University of Milan; Milan, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.affiliation: VA Boston Healthcare System and the Department of Medicine; Boston University School of Medicine; Boston, MA USA.
authors.forename: Pantel S
authors.initials: PS
authors.lastname: Vokonas
authors.affiliation: Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
authors.forename: Petros
authors.initials: P
authors.lastname: Koutrakis
authors.affiliation: Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects*; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013925:Thromboplastin / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013925:Thromboplastin
keywords: air pollution; effect modification; elderly; gene-specific DNA methylation; mediation analysis; traffic