Long-term outdoor air pollution and DNA methylation in circulating monocytes: results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

BackgroundDNA 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).MethodsOne-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.ResultsAt 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0202-4) contains supplementary material, which is available to authorized users.

Genome-wide transcriptional analysis of cardiovascular-related genes and pathways induced by PM2.5 in human myocardial cells

“…Among the significant upregulation pathways, the NF-κB signaling pathway and chemokine signaling pathway were reported in ultrafine particle toxicity. Ultrafine particles could induce phagocytic activity in immune cell (Pinsino et al 2015), inflammation, and DNA damage in circulating monocytes (Chi et al 2016). On the other hand, among the significant downregulation pathways, the TGF-β signaling pathway has been documented in particle-induced toxicity (Xie et al 2015).…”

Oxidative stress and inflammation mediate the effect of air pollution on cardio‐ and cerebrovascular disease: A prospective study in nonsmokers

“…DNA methylation (DNAm) dysregulation, in turn, was described in relation to long‐term air pollution exposure. Air pollution has been hypothesized to be related to CCVD through deregulation of genes coding for both pro‐inflammatory and anti‐inflammatory cytokines (Chi et al, ). Also, reduced methylation of mitochondrial DNA (that is one of the primary targets of oxidative stress) was associated with exposure to fine particulate PM 2.5 and modified the adverse relationships between PM 2.5 exposure and heart rate variability outcomes (Byun et al, ).…”

Reduced mouse allergen is associated with epigenetic changes in regulatory genes, but not mouse sensitization, in asthmatic children

“…We believe these associations are gene specific as there is substantial evidence that epigenetic regulation of both FOXP3 and IFNγ is associated with clinically relevant outcomes (Liu, Ballaney et al 2008, Brand, Kesper et al 2012, Kohli, Garcia et al 2012, Niedzwiecki, Zhu et al 2012, Runyon, Cachola et al 2012, Tang, Levin et al 2012). There is more limited evidence to suggest that differences in global methylation instead may explain outcomes related to exposure to cigarettes and air pollution (Breton, Byun et al 2009, Lee, Jaffar et al 2015, Breton, Yao et al 2016) and allergic sensitization(Sordillo, Lange et al 2013) in some, but not other (Chi, Liu et al 2016), studies.…”