title: Associations between serum perfluoroalkyl acids and LINE-1 DNA methylation.
abstract: Perfluoroalkyl acids (PFAAs) are persistent, synthetic compounds that are used in a number of consumer products. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been associated with cardiovascular risk factors, and changes in gene expression and DNA methylation in animals and cellular systems. However, whether PFAA exposure is associated with LINE-1 DNA methylation, a potential marker of cardiovascular risk, in humans remains unknown. We sought to evaluate the cross-sectional associations between serum PFAAs and LINE-1 DNA methylation in a population highly exposed to PFOA. We measured serum PFAAs twice four to five years apart in 685 adult participants (47% male, mean age±SD=42±11years). We measured percent LINE-1 DNA methylation in peripheral blood leukocytes at the second time point (follow-up), and estimated absolute differences in LINE-1 methylation associated with an interquartile (IQR) shift in mean PFAA serum levels. IQR increases in mean serum PFOA, PFOS, perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were associated with differences of -0.04 (p=0.16), 0.20 (p=0.001), 0.06 (p=0.19), and 0.02 (p=0.57), respectively, in % LINE-1 methylation at follow-up after adjustment for potential confounders. We observed a monotonic increase in LINE-1 DNA methylation across tertiles of PFOS and PFNA (ptrend=0.02 for both associations), but not across tertiles of PFOA or PFHxS (ptrend=0.71 and 0.44, respectively). In summary, serum PFOS was associated with LINE-1 methylation, while serum PFOA, PFHxS, and PFNA were not. Additional research is needed to more precisely determine whether these compounds are epigenetically active.
authors.affiliation: Department of Epidemiology, Center for Environmental Health and Technology, Brown University, Providence, RI, USA.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Watkins
authors.affiliation: Department of Epidemiology, Center for Environmental Health and Technology, Brown University, Providence, RI, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wellenius
authors.affiliation: Department of Epidemiology, Center for Environmental Health and Technology, Brown University, Providence, RI, USA.
authors.forename: Rondi A
authors.initials: RA
authors.lastname: Butler
authors.affiliation: Program in Public Health, University of California, Irvine, CA, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Bartell
authors.affiliation: Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Fletcher
authors.affiliation: Department of Epidemiology, Center for Environmental Health and Technology, Brown University, Providence, RI, USA; Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA. Electronic address: karl_kelsey@brown.edu.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
mesh_terms: D000328:Adult; D017738:Alkanesulfonic Acids / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002210:Caprylates / Q000097:blood*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005466:Fluorocarbons / Q000097:blood*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D017738:Alkanesulfonic Acids; D015415:Biomarkers; D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid; C078626:perflexane
keywords: 8 carbon chain, referring to perfluorooctanoic acid; BMI; C8; CDC; CVD; Cardiovascular disease; Centers for Disease Control and Prevention; DNA methylation; Epigenetics; HDL-C; IQR; IRB; Institutional Review Board; LDL-C; LINE-1; NHANES; NIOSH; National Health and Nutrition Examination Survey; National Institute for Occupational Safety and Health; PFAA; PFHxS; PFNA; PFOA; PFOS; PPAR; Perfluorooctane sulfonate; Perfluorooctanoic acid; body mass index; cardiovascular disease; high density lipoprotein cholesterol; interquartile range; long interspersed nuclear element 1; low density lipoprotein cholesterol; perfluoroalkyl acid; perfluorohexane sulfonate; perfluorononanoic acid; perfluorooctane sulfonate; perfluorooctanoic acid; peroxisome-proliferator activated receptor