Abstract
We used a randomized crossover experiment to estimate the effects of ozone (vs. clean air) exposure on genome-wide DNA methylation of target bronchial epithelial cells, using 17 volunteers, each randomly exposed on two separated occasions to clean air or 0.3-ppm ozone for two hours. Twenty-four hours after exposure, participants underwent bronchoscopy to collect epithelial cells whose DNA methylation was measured using the Illumina 450 K platform. We performed global and regional tests examining the ozone versus clean air effect on the DNA methylome and calculated Fisher-exact p-values for a series of univariate tests. We found little evidence of an overall effect of ozone on the DNA methylome but some suggestive changes in PLSCR1, HCAR1, and LINC00336 DNA methylation after ozone exposure relative to clean air. We observed some participant-to-participant heterogeneity in ozone responses.
Highlights
We used a randomized crossover experiment to estimate the effects of ozone exposure on genome-wide DNA methylation of target bronchial epithelial cells, using 17 volunteers, each randomly exposed on two separated occasions to clean air or 0.3-ppm ozone for two hours
In one s tudy[13], exposure to traffic-related pollutants was associated with reduced lung function in elderly men and epigenetic changes in genes related to inflammation and immunity were proposed to modify the air pollution-lung function association
Increased air pollution was significantly associated with changes in DNA methylation of several genes, including those involved in inflammation[14]
Summary
We used a randomized crossover experiment to estimate the effects of ozone (vs. clean air) exposure on genome-wide DNA methylation of target bronchial epithelial cells, using 17 volunteers, each randomly exposed on two separated occasions to clean air or 0.3-ppm ozone for two hours. Exposure to air pollution has been associated in several recent non-randomized studies with epigenetic changes, especially DNA methylation. Age Body mass index Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Heart rate (beats/min) Gender Male Female Race White Non-white Because all these studies are non-randomized cohort studies in which changes in ambient pollutant levels are associated with epigenetic changes, it is difficult to claim a causal relationship between air pollutant exposure and epigenetic changes. A recent randomized controlled human exposure study measured DNA methylation changes in T helper cells found in blood and reported changes in methylation in genes involved in mitochondrial oxidative energy metabolism in subjects exposed to particulate air p ollution[16]. We report the results of a random exposure study in which human volunteers were randomly exposed to either 0.3-ppm ozone or clean air on two occasions separated by several weeks. Because of the small sample size of the experiment, we eschew standard asymptotic inference assuming Student’s t-distributions under the null hypothesis, and instead capitalize on exact randomization-based inference
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