Global DNA Hypomethylation Is Associated with High Serum-Persistent Organic Pollutants in Greenlandic Inuit
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Background: Persistent organic pollutants (POPs) may influence epigenetic mechanisms; therefore, they could affect chromosomal stability and gene expression. DNA methylation, an epigenetic mechanism, has been associated with cancer initiation and progression. Greenlandic Inuit have some of the highest reported POP levels worldwide. Objective: Our aim in this study was to evaluate the relationship between plasma POPs concentrations and global DNA methylation (percent 5-methylcytosine) in DNA extracted from blood samples from 70 Greenlandic Inuit. Blood samples were collected under the Arctic Monitoring and Assessment Program and previously analyzed for a battery of POPs. Methods: We used pyrosequencing to estimate global DNA methylation via Alu and LINE-1 assays of bisulfite-treated DNA. We investigated correlations between plasma POP concentrations and global DNA methylation via correlation coefficients and linear regression analyses. Results: We found inverse correlations between percents methylcytosine and many of the POP concentrations measured. Linear regressions, adjusting for age and cigarette smoking, showed statistically significant inverse linear relationships mainly for the Alu assay for p,p′-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; β = −0.26), p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene; β = −0.38], β-hexachlorocyclohexane (β = −0.48), oxychlordane (β = −0.32), α-chlordane (β = −0.75), mirex (β = −0.27), sum of polychlorinated biphenyls (β = −0.56), and sum of all POPs (β = −0.48). Linear regressions for the LINE-1 assay showed β estimates of similar magnitudes to those using the Alu assay, however, none was statistically significant. Conclusions: This is the first study to investigate environmental exposure to POPs and DNA methylation levels in a human population. Global methylation levels were inversely associated with blood plasma levels for several POPs and merit further investigation.
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A similar trend was observed in a second population of healthy Koreans for NDL PCB 153, 183, and 187 and in a population of Greenlandic Inuits.
“A similar trend was observed in a second population of healthy Koreans for NDL PCB 153, 183, and 187 [ 37 ] and in a population of Greenlandic Inuits [ 38 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [38]
DL and NDL PCBs have opposing actions on DNA methylation, with DL PCBs shifting the balance toward DNA hypermethylation and NDL PCBs favoring DNA hypomethylation.
“There is evidence to suggest that the DL and NDL PCBs have opposing actions on DNA methylation, with DL PCBs shifting the balance toward DNA hypermethylation, as was observed in the Sweden study [ 39 ], and NDL PCBs favoring DNA hypomethylation as observed in the Korean and Inuit studies [ 36 , 38 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [38]
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LINE ‐1 hypomethylation in spermatozoa is associated with Bisphenol A exposure
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Self-citation
- Authors
- Rusiecki, J. A., Baccarelli, A., Bollati, V., Tarantini, L., Moore, L. E., & Bonefeld-Jorgensen, E. C.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- University of Milan (IT)
- National Institutes of Health (US)
- University of Aarhus, Unit of Cellular and Molecular Toxicology, Centre of Arctic Environmental Medicine, Institute of Public Health, University of Aarhus, Aarhus, Denmark
- Corresponding author
- Rusiecki, Jennifer A.
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-07-16
- Volume
- 116
- Issue
- 11
- Pages
- 1547-1552
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC2592276
- OpenAlex
- W2087008478
- Cited by
- 352
- References
- 51
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 15 · 2021: 24 · 2020: 21 · 2019: 24 · 2018: 19 · 2017: 23 · 2016: 26 · 2015: 30 · 2014: 23 · 2013: 32 · 2012: 34
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 3453 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- Uniformed Services University of the Health Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Keywords
- persistent organic pollutants, global DNA methylation, DNA hypomethylation, Greenlandic Inuit, p,p'-DDE, p,p'-DDT, polychlorinated biphenyls, organochlorine pesticides, Alu elements, LINE-1 elements, epigenetics, environmental exposure, plasma concentration
- MeSH terms
- Adult, Aged, DNA, Environmental Pollutants, Inuit, Female, Greenland, Humans, Male, Middle Aged, Organic Chemicals, Pesticides, DNA Methylation
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