Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefighters

By Jaclyn M Goodrich, Miriam M Calkins, Alberto J Caban-Martinez, Todd Stueckle, Casey Grant, Antonia M Calafat, Amy Nematollahi, Alesia M Jung, Judith M Graber, Timothy Jenkins, Angela L Slitt, Alisa Dewald, Julianne Cook Botelho, Shawn Beitel, Sally Littau, John Gulotta, Darin Wallentine, Jeff Hughes, Charles Popp, and Jefferey L Burgess
November 2, 2021
DOI: 10.2217/epi-2021-0225

Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

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