Global DNA hypermethylation is associated with high serum levels of persistent organic pollutants in an elderly population.
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.
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
Lars
L
Lind
Johanna
J
Penell
Karin
K
Luttropp
Louise
L
Nordfors
Anne-Christine
AC
Syvänen
Tomas
T
Axelsson
Samira
S
Salihovic
Bert
B
van Bavel
Tove
T
Fall
Erik
E
Ingelsson
P Monica
PM
Lind
D000368:Aged; D003430:Cross-Sectional Studies; D019175:DNA Methylation / Q000187:drug effects*; D003633:Dichlorodiphenyl Dichloroethylene / Q000097:blood / Q000633:toxicity; D004147:Dioxins / Q000097:blood* / Q000633:toxicity; D004785:Environmental Pollutants / Q000097:blood* / Q000633:toxicity; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000097:blood* / Q000633:toxicity; D006801:Humans; D008297:Male; D010575:Pesticides / Q000097:blood* / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000097:blood*; D000072317:Polychlorinated Dibenzodioxins / Q000097:blood* / Q000633:toxicity; D011446:Prospective Studies; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism
D004147:Dioxins; D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D010575:Pesticides; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C511295:2,2',4,4'-tetrabromodiphenyl ether; D003633:Dichlorodiphenyl Dichloroethylene; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl
2, 2-Bis (4-chlorophenyl)-1, 1-dichloroethene; 2,3,7,8-Tetrachlorodibenzo-p-dioxin; Ah; Aryl hydrocarbon; BDE; CI; DNA; DNA methylation; Elderly; HCB; HRGC; HRMS; HWP; Hardy–Weinberg principle; Hexachlorobenzene; LUMA; Luminometric Methylation Assay; OC; OCDD; PCBs; PIVUS; POP; Persistent organic pollutants; Prospective Investigation of the Vasculature in Uppsala Seniors; RNA; SNP; TCDD; TEQ; TNC; Trans-nonachlordane; WHO; World Health Organization; brominated biphenyl ether; confidence interval; deoxyribonucleic acid; high-resolution gas chromatography; high-resolution mass spectrometry; octachlorodibenzo-p-dioxin; organochlorine; p,p′-DDE; persistent organic pollutants; polychlorinated biphenyls; ribonucleic acid; single nucleotide polymorphism; toxic equivalency