Abstract
BackgroundChanges in DNA methylation have been associated with traffic-related air pollution in observational studies, but the specific mechanisms and temporal dynamics therein have not been explored in a controlled study of asthmatics. In this study, we investigate short-term effects of diesel exhaust inhalation on DNA methylation levels at CpG sites across the genome in circulating blood in asthmatics.MethodsA double-blind crossover study of filtered air and diesel exhaust exposures was performed on sixteen non-smoking asthmatic subjects. Blood samples were collected pre-exposure, and then 6 and 30 hours post-exposure. Peripheral blood mononuclear cell DNA methylation was interrogated using the Illumina Infinium HumanMethylation450 Array. Exposure-related changes in DNA methylation were identified. In addition, CpG sites overlapping with Alu or LINE1 repetitive elements and candidate microRNA loci were also analyzed.ResultsDNA methylation at 2827 CpG sites were affected by exposure to diesel exhaust but not filtered air; these sites enriched for genes involved in protein kinase and NFkB pathways. CpG sites with significant changes in response to diesel exhaust exposure primarily became less methylated, with a site residing within GSTP1 being among the significant hits. Diesel exhaust-associated change was also found for CpG sites overlapping with Alu and LINE1 elements as well as for a site within miR-21.ConclusionShort-term exposure to diesel exhaust resulted in DNA methylation changes at CpG sites residing in genes involved in inflammation and oxidative stress response, repetitive elements, and microRNA. This provides plausibility for the role of DNA methylation in pathways by which airborne particulate matter impacts gene expression and offers support for including DNA methylation analysis in future efforts to understand the interactions between environmental exposures and biological systems.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-014-0071-3) contains supplementary material, which is available to authorized users.
Highlights
Changes in DNA methylation have been associated with traffic-related air pollution in observational studies, but the specific mechanisms and temporal dynamics therein have not been explored in a controlled study of asthmatics
Using PCA, a dimensionality reduction technique, we decomposed the data to a set of 95 principal components (PCs), each of which explained a dominant and independent pattern of variation across the samples; we assessed the relative contribution of each principal component to the overall variance
PCA facilitated linear decomposition of the data, allowing identification of data dimension that significantly captured the association between DNA methylation change and exposure to diesel exhaust (DE)
Summary
Changes in DNA methylation have been associated with traffic-related air pollution in observational studies, but the specific mechanisms and temporal dynamics therein have not been explored in a controlled study of asthmatics. We investigate short-term effects of diesel exhaust inhalation on DNA methylation levels at CpG sites across the genome in circulating blood in asthmatics. Exposure to air pollutants is an increasing public health concern that has been associated with adverse health effects focused on cardiovascular and respiratory diseases [1,2,3]. The hazardous effects of DE is associated with asthma susceptibility and severity; for example, evidence links exposure to diesel exhaust with worse lung functions and increased airway resistance [20,21]. It has been hypothesized that exposure to DE may be partly responsible for the increase in allergic diseases in industrialized nations [22]
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