TY - JOUR
T1 - Global DNA hypomethylation is associated with high serum-persistent organic pollutants in Greenlandic inuit
AU - Rusiecki, Jennifer A.
AU - Baccarelli, Andrea
AU - Bollati, Valentina
AU - Tarantini, Letizia
AU - Moore, Lee E.
AU - Bonefeld-Jorgensen, Eva C.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Global methylation
KW - Greenland
KW - Hypomethylation
KW - Inuit
KW - Organochlorines
KW - PCBs
KW - POPs
KW - Persistent organic pollutants
KW - Pesticides
KW - Polychlorinated biphenyls
KW - Serum
UR - http://www.scopus.com/inward/record.url?scp=58849158772&partnerID=8YFLogxK
U2 - 10.1289/ehp.11338
DO - 10.1289/ehp.11338
M3 - Article
C2 - 19057709
AN - SCOPUS:58849158772
SN - 0091-6765
VL - 116
SP - 1547
EP - 1552
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
IS - 11
ER -