Association of DNA methylation in circulating CD4+T cells with short-term PM2.5 pollution waves: A quasi-experimental study of healthy young adults.

BACKGROUND: Fine particulate matter (PM2.5) is a modifiable environmental risk factor with established adverse effects on human health. However, associations between acute PM2.5 fluctuation and DNA methylation remain unknown. METHODS: A quasi-experimental study utilizing naturally occurring PM2.5 pollution waves (PPWs) was conducted on 32 healthy young adults. Repeated follow-up measurements were performed and participants served as their own controls before, during, and after PPWs. Exposure measurements including indoor and ambient PM2.5 levels, and equivalent personal PM2.5 exposure were further estimated based on the time-location information. DNA methylation profiles of circulating CD4+T cells were obtained using Illumina HumanMethylationEPIC BeadChip. Linear mixed-effect models were applied to estimate the associations between two scenarios (during-PPWs vs. pre-PPWs periods and during-PPWs vs. post-PPWs periods) and methylation level of each CpG site. We further validated their associations with the personal PM2.5 exposure, and GO and KEGG analyses and mediation analysis were conducted accordingly. RESULTS: Data from 26 participants were included in final analysis after quality control. Short-term high PM2.5 exposure was associated with DNA methylation changes of participants. Nine differently methylated CpG sites were not only significantly associated with PPWs periods but also with personal PM2.5 exposure in 24-h prior to the health examinations (p < 0.01). Gene ontology analysis found that five sites were associated with two pathways relating to membrane protein synthesis. PM2.5-related changes in CpG sites were mediated by sP-selectin, 8-isoPGF2α, EGF, GRO, IL-15, and IFN-α2, with mediated proportions ranging from 9.65% to 23.40%. CONCLUSIONS: This is the first quasi-experimental study showing that short-term high PM2.5 exposure could alter the DNA methylation of CD4+T cells, which provided valuable information for further exploring underlying biological mechanisms and epigenetic biomarkers for PM2.5-related acute health effects.