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Global DNA hypermethylation is associated with high serum levels of persistent organic pollutants in an elderly population
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
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2013 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 59, 456-461 p.Article in journal (Refereed) Published
Abstract [en]

Dioxin exposure has experimentally been associated with changes in DNA methylation, an epigenetic change that is associated with disease. The present study aims to investigate if serum levels of dioxin and other persistent environmental pollutants are related to global DNA methylation in a human sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (all aged 70), global DNA methylation was measured by the Luminometric Methylation Assay in 524 subjects. Twenty-three different POPs, including 16 PCBs, five pesticides, one dioxin (OCDD) and one brominated flame retardant (BDE47) were analysed by HRGC/HRMS. Ten single nucleotide polymorphisms (SNPs) in the Aryl hydrocarbon (Ah)-receptor were analysed by mini-sequencing. High levels of toxic equivalency (TEQ) for PCBs and dioxin were associated with DNA hypermethylation (p=0.030). This was mainly attributed to coplanar non-ortho PCBs. While no significant associations were found between DNA methylation and SNPs in the Ah-receptor, an interaction was found between the SNP rs2237297 and TEQ so that TEQ was associated with hypermethylation (p=0.009) only in subjects with one G-allele (n=103). Also high levels of the PCB126 congener, the OCDD, and the pesticide metabolite p,p'-DDE were related to DNA hypermethylation (p=0.01, 0.03 and 0.003, respectively). In conclusion, in a sample of elderly subjects, high TEQ including PCBs and the dioxin OCDD and high serum levels of PCB126, OCDD, and p,p'-DDE were related to global DNA hypermethylation in a cross-sectional analysis.

Place, publisher, year, edition, pages
2013. Vol. 59, 456-461 p.
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Medical Genetics
URN: urn:nbn:se:uu:diva-207899DOI: 10.1016/j.envint.2013.07.008ISI: 000324901000049PubMedID: 23933504OAI: oai:DiVA.org:uu-207899DiVA: diva2:650237
Available from: 2013-09-20 Created: 2013-09-20 Last updated: 2016-01-26Bibliographically approved

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Lind, LarsPenell, JohannaSyvänen, Ann-ChristineAxelsson, TomasFall, ToveIngelsson, ErikLind, P Monica
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Cardiovascular epidemiologyOccupational and Environmental MedicineMolecular MedicineScience for Life Laboratory, SciLifeLabMolecular epidemiology
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