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 (PM) 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 PM 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 PM. Blood genome-wide 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 PM levels on genome-wide DNA methylation.

Results: There was a drastic contrast for PM exposure levels in the two scenarios (24-h averages: 53.1 and 24.3 μg/m). 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 PM 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 PM 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 PM exposure.