Short-term exposure to fine particulate air pollution and genome-wide DNA methylation: A randomized, double-blind, crossover trial

Background: Previous studies have associated fine particulate (PM2.5) exposure with changes in gene-specific DNA methylation. However, the evidence was still limited and inconsistent in genome-wide DNA methylation. Objective: To examine the impact of short-term PM2.5 exposure on genome-wide DNA methylation. Methods: We designed a randomized, double-blind, crossover trial among 36 healthy young adults in Shanghai, China. A two-stage intervention with alternative use of real and sham air purifiers in dormitory rooms for consecutive 9 days were conducted to create natural low and high exposure scenarios of PM2.5. Blood genomewide DNA methylation was analyzed using the Illumina Infinium Human Methylation EPIC BeadChip (850k). Mixed-effect models were used to evaluate the impacts of changes in PM2.5 levels on genome-wide DNA methylation. Results: There was a drastic contrast for PM2.5 exposure levels in the two scenarios (24-h averages: 53.1 and 24.3 mu g/m(3)). Between the high and low exposure groups, methylation levels were changed significantly with a false discovery rate < 0.01 at 49 CpG loci, of which 31 CpG sites were annotated to the specific genes. DNA methylation of these annotated genes were elevated in response to increased PM2.5 exposure, which were implicated in insulin resistance, glucose and lipid metabolism, inflammation, oxidative stress, platelet activation, and cell survival and apoptosis. Conclusions: Our results provided novel biological pathways linking ambient PM2.5 exposure to systemic adverse response through variations in DNA methylation and reinforced the hypothesized role of epigenetics in the development of cardiometabolic diseases induced by PM2.5 exposure.