1931

Background: Current research suggests that short- and intermediate- term exposure to ambient particulate matter is associated with global and gene-specific DNA methylation (DNAm), but little is known regarding the changes in epigenome-wide caused by particulate elements (PEs). Additionally, the potential pathways remain unknown.Objective: We evaluated short- to intermediate-term associations between ambient PEs and DNAm in epigenome-wide and identified potential biological pathways.Method: We collected whole blood samples from 691 elderly men in the Normative Aging Study (1999-2013) and measured epigenome-wide DNAm with the Illumina Infinium HumanMethylation450 BeadChip. Ambient PEs were measured daily at a fixed monitoring station and 5 different moving averages from short- to intermediate-term (current day to 28-day) were considered. Linear quantile mixed models were used to estimate the associations between 15 elements and DNAm (N=1, 262 visits), adjusting for fine particle mass, cell type, batch effects, age, body mass index, smoking, etc. Pathway analysis was also performed to explore the potential biologic mechanisms.Results: Short- to intermediate-term exposure to PEs was significantly associated with epigenome-wide DNAm, especially for 28-d moving average. We observed different Bonferroni significant CpGs for different PE, most of them related with aluminum, iron, silicon, lead, and, calcium. The pathway analyses suggest that the detrimental effects might be relevant to cell cycle, biosynthetic process, and signal transduction. We also found that there were several common genes significantly associated with calcium, silicon and lead, such as, neurodegenerative disease related gene tubulin folding cofactor D.Conclusions: Ours is the first study that find short- to intermediate-term effects on DNAm in epigenome-wide by ambient PEs, especially elements associated with road dust, oil combustion, and wood burning. Our findings provide insight into potential mechanistic pathways.