Global DNA Hypomethylation Is Associated with High Serum-Persistent Organic Pollutants in Greenlandic Inuit

Abstract

BackgroundPersistent 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.ObjectiveOur 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.MethodsWe 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.ResultsWe 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.ConclusionsThis 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.

Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood: Prospective results from a folate-replete population

“…However, we used the most technologically advanced and validated methods currently available for LINE-1 methylation analysis and have already demonstrated a relationship between higher LINE-1 and male sex and several other obesity-related risk factors in offspring in early life. 17 This method for LINE-1 methylation analysis has been shown in previous investigations to be sensitive to environmental and host-related factors, including age, 18 sex, 16,19 smoking 20 and tobacco smoke components, 21 physical activity 22 and environmental pollution. [23][24][25][26] Also, we measured DNA methylation only in blood DNA and we cannot exclude that methylation changes due to dietary components might be present in other tissues in the same individuals.…”

DNA methylation in white blood cells

“…LINE-1, Alu and AluYb8 methylation did not differ between current and never/former smokers. 17,21,37,41,57,69 Some studies recruited small number of subjects; however, the overall consistency of the results suggests that genomic DNA methylation levels are not affected by active smoking exposure in adulthood.…”

“…41,57 In 70 Greenlandic Inuit, a population presenting some of the highest reported levels of POP worldwide, a significant inverse linear relationship was found for DDT, DDE, β-hexachlorocyclohexane, oxychlordane, α-chlordane, mirex, several PCBs and the sum of all persistent organic pollutants with Alu methylation. 57 However, as the exposure levels in Greenlandic Inuit are much higher than those in the US general population, it is unclear whether the findings apply to other populations with lower exposures. A study in Korea 41 found that most organochlorine (OC) pesticides were inversely and significantly associated with Alu methylation.…”

Organochlorine Pesticides in Human Serum

“…The serum concentrations of HCB, -HCH, p,p'-DDE, oxychlordane, and trans-nonachlor increased with increasing age and were significantly higher in the 60 years and older age group (CDC, 2005;Patterson et al, 2009). Because the general population was exposed to these pesticides by eating contaminated fatty food such as fish, an Inuit population in Greenland showed high levels of exposure (Rusiecki et al, 2008). Serum samples were collected from 70 Greenlandic Inuit (61 men, 9 women) under the Arctic Monitoring and Assessment Program (AMAP) in 1997-1998.…”