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Associations between serum concentrations of perfluoroalkyl substances and DNA methylation in women exposed through drinking water : A pilot study in Ronneby, Sweden

Xu, Yiyi LU ; Jurkovic-Mlakar, Simona ; Lindh, Christian H. LU orcid ; Scott, Kristin LU ; Fletcher, Tony ; Jakobsson, Kristina LU and Engström, Karin LU (2020) In Environment International 145.
Abstract

Background: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFAS is via epigenetic changes, such as DNA methylation. However, few studies have evaluated associations between PFAS exposure and DNA methylation among adults, and data is especially scarce for women. Furthermore, exposure to environmental pollutants has been associated with epigenetic age acceleration, but no studies have yet evaluated whether PFAS is associated with epigenetic age acceleration. Objectives: To investigate whether exposure to PFAS is associated with alteration of DNA methylation and epigenetic age acceleration among women. Methods: In this observational pilot... (More)

Background: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFAS is via epigenetic changes, such as DNA methylation. However, few studies have evaluated associations between PFAS exposure and DNA methylation among adults, and data is especially scarce for women. Furthermore, exposure to environmental pollutants has been associated with epigenetic age acceleration, but no studies have yet evaluated whether PFAS is associated with epigenetic age acceleration. Objectives: To investigate whether exposure to PFAS is associated with alteration of DNA methylation and epigenetic age acceleration among women. Methods: In this observational pilot study, 59 women (aged 20–47 years at enrollment in 2014) from Ronneby, Sweden, an area with historically high PFAS exposure due to local drinking water contamination, were divided into three PFAS exposure groups (low, medium, and high). Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip. Ingenuity Pathway Analysis was used for in silico functional assessment. Epigenetic age acceleration was derived from the DNA methylation data using Horvath's epigenetic skin and blood clock. Results: 117 differentially methylated positions (q < 0.017) and one near-significantly differentially methylated region (S100A13, FWER = 0.020) were identified. In silico functional analyses suggested that genes with altered DNA methylation (q < 0.05) were annotated to cancer, endocrine system disorders, reproductive system disease, as well as pathways such as estrogen receptor signaling, cardiac hypertrophy signaling, PPARα/RXRα activation and telomerase signaling. No differences in epigenetic age acceleration between PFAS exposure groups were noted (p = 0.43). Conclusion: The data suggests that PFAS exposure alters DNA methylation in women highly exposed to PFAS from drinking water. The observed associations should be verified in larger cohorts, and it should also be further investigated whether these changes in methylation also underlie potential phenotypic changes and/or adverse health effects of PFAS.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Environmental pollutant, EPIC chip, Epigenetic aging, Epigenetics, Perfluoroalkyl substance, PFAS
in
Environment International
volume
145
article number
106148
publisher
Elsevier
external identifiers
  • pmid:33007577
  • scopus:85091739307
ISSN
0160-4120
DOI
10.1016/j.envint.2020.106148
language
English
LU publication?
yes
id
f7bc3704-18e6-4ec8-8dac-3c45f04c1cad
date added to LUP
2020-10-27 11:41:30
date last changed
2024-04-17 17:51:45
@article{f7bc3704-18e6-4ec8-8dac-3c45f04c1cad,
  abstract     = {{<p>Background: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFAS is via epigenetic changes, such as DNA methylation. However, few studies have evaluated associations between PFAS exposure and DNA methylation among adults, and data is especially scarce for women. Furthermore, exposure to environmental pollutants has been associated with epigenetic age acceleration, but no studies have yet evaluated whether PFAS is associated with epigenetic age acceleration. Objectives: To investigate whether exposure to PFAS is associated with alteration of DNA methylation and epigenetic age acceleration among women. Methods: In this observational pilot study, 59 women (aged 20–47 years at enrollment in 2014) from Ronneby, Sweden, an area with historically high PFAS exposure due to local drinking water contamination, were divided into three PFAS exposure groups (low, medium, and high). Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip. Ingenuity Pathway Analysis was used for in silico functional assessment. Epigenetic age acceleration was derived from the DNA methylation data using Horvath's epigenetic skin and blood clock. Results: 117 differentially methylated positions (q &lt; 0.017) and one near-significantly differentially methylated region (S100A13, FWER = 0.020) were identified. In silico functional analyses suggested that genes with altered DNA methylation (q &lt; 0.05) were annotated to cancer, endocrine system disorders, reproductive system disease, as well as pathways such as estrogen receptor signaling, cardiac hypertrophy signaling, PPARα/RXRα activation and telomerase signaling. No differences in epigenetic age acceleration between PFAS exposure groups were noted (p = 0.43). Conclusion: The data suggests that PFAS exposure alters DNA methylation in women highly exposed to PFAS from drinking water. The observed associations should be verified in larger cohorts, and it should also be further investigated whether these changes in methylation also underlie potential phenotypic changes and/or adverse health effects of PFAS.</p>}},
  author       = {{Xu, Yiyi and Jurkovic-Mlakar, Simona and Lindh, Christian H. and Scott, Kristin and Fletcher, Tony and Jakobsson, Kristina and Engström, Karin}},
  issn         = {{0160-4120}},
  keywords     = {{Environmental pollutant; EPIC chip; Epigenetic aging; Epigenetics; Perfluoroalkyl substance; PFAS}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Environment International}},
  title        = {{Associations between serum concentrations of perfluoroalkyl substances and DNA methylation in women exposed through drinking water : A pilot study in Ronneby, Sweden}},
  url          = {{http://dx.doi.org/10.1016/j.envint.2020.106148}},
  doi          = {{10.1016/j.envint.2020.106148}},
  volume       = {{145}},
  year         = {{2020}},
}