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

Previous studies have associated fine particulate (PM_2.5) exposure with changes in gene-specific DNA methylation. However, the evidence was still limited and inconsistent in genome-wide DNA methylation.

To examine the impact of short-term PM_2.5 exposure on genome-wide DNA methylation.

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_2.5. 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_2.5 levels on genome-wide DNA methylation.

There was a drastic contrast for PM_2.5 exposure levels in the two scenarios (24-h averages: 53.1 and 24.3 μg/m³). 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_2.5 exposure, which were implicated in insulin resistance, glucose and lipid metabolism, inflammation, oxidative stress, platelet activation, and cell survival and apoptosis.

Our results provided novel biological pathways linking ambient PM_2.5 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 PM_2.5 exposure.