Volume 10 Supplement 1
Genomewide DNA methylation dynamics upon diesel exhaust exposure in asthmatics
© Jiang et al; licensee BioMed Central Ltd. 2014
Published: 3 March 2014
Particulate air pollution can induce epigenetic changes and regulate gene expression relevant to the pathophysiology of asthma and allergic diseases. Recently, epidemiologic data suggests that there are observable acute effects of air pollution on peripheral blood DNA methylation levels of genomewide Alu and LINE-1 repeat elements, as well as certain genes involved in oxidative stress response and innate immunity. In this study, we hypothesized that in a controlled exposure setting, diesel exhaust (as a model of particulate air pollution) can induce DNA methylation changes that are detectable on the genomewide level.
We recruited 16 subjects with asthma, and/or airway hyper-responsiveness. They were exposed to both diesel exhaust (DE) and filtered air (FA) following a randomized crossover design. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, 6 hours, and 30 hours post-exposure. Methylation at 415,382 CpG sites covering 39,136 genes was measured using the Illumina Infinium 450K bead chip methylation array. To detect effects of the diesel exposure, we conducted a principal component analysis (PCA) , resulting in principal components with common patterns of methylation variation across samples. Using this method we were able to pinpoint one principal component that was significantly associated with diesel exhaust exposure, from which we then selected a subset of probes that possessed that specific pattern of variation.
These results suggest that short-term exposure to diesel exhaust in a controlled setting has minimal but detectable effects on a genomewide level in PBMCs. We are currently applying mixed effects modeling and intraclass correlation to our identified hits to further substantiate the association of these hit probes to the treatment variable.
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