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Low-Level Environmental Cadmium Exposure is Associated with DNA Hypomethylation in Argentinean Women.

Hossain, Mohammad Bakhtiar; Vahter, Marie; Concha, Gabriela and Broberg Palmgren, Karin LU (2012) In Environmental Health Perspectives 120(6). p.879-884
Abstract
Background: Cadmium, a common food pollutant, alters DNA methylation in vitro. Epigenetic effects might therefore partly explain cadmium's toxicity, including carcinogenicity, but human data on epigenetic effects are lacking. Objectives: To evaluate effects of dietary cadmium exposure on DNA methylation, considering other environmental exposures, genetic predisposition, and gene expression.



Methods: Concentrations of cadmium, arsenic, selenium and zinc in blood and urine of nonsmoking women (N=202) from the Northern Argentinean Andes were measured by ICP-MS. Methylation in CpG islands of LINE1 (proxy for global DNA methylation) and promoter regions of p16 (CDKN2A) and MLH1 in peripheral blood were measured by bisulfite... (More)
Background: Cadmium, a common food pollutant, alters DNA methylation in vitro. Epigenetic effects might therefore partly explain cadmium's toxicity, including carcinogenicity, but human data on epigenetic effects are lacking. Objectives: To evaluate effects of dietary cadmium exposure on DNA methylation, considering other environmental exposures, genetic predisposition, and gene expression.



Methods: Concentrations of cadmium, arsenic, selenium and zinc in blood and urine of nonsmoking women (N=202) from the Northern Argentinean Andes were measured by ICP-MS. Methylation in CpG islands of LINE1 (proxy for global DNA methylation) and promoter regions of p16 (CDKN2A) and MLH1 in peripheral blood were measured by bisulfite PCR pyrosequencing. Genotyping (N=172) for DNMT1 (rs10854076, rs2228611) and DNMT3B (rs2424913, rs2424932) was performed with SequenomTM; and gene expression (N=90) with DirectHyb HumanHT-12 v3.0.



Results: Cadmium exposure was low: median concentrations in blood and urine were 0.36 and 0.23 µg/L, respectively. Urinary cadmium (ln transformed) was inversely associated with LINE1 methylation (β=-0.50, p=0.0070; β=-0.44, p=0.026 adjusted for age and coca chewing), but not with p16 or MLH1 methylation. Both DNMT1 rs10854076 and DNMT1 rs2228611 polymorphisms modified associations between urinary cadmium and LINE1 (p-values for interaction in adjusted models were 0.045 and 0.064, respectively). The rare genotypes demonstrated stronger hypomethylation with increasing urinary cadmium concentrations. Cadmium was inversely associated with DNMT3B (rs -0.28, p=0.0086), but not with DNMT1 expression (rs -0.075, p=0.48).



Conclusion: Environmental cadmium exposure was associated with DNA hypomethylation in peripheral blood and DNMT1 genotypes modified this association. The role of epigenetic modifications in cadmium-associated diseases needs clarification. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Environmental Health Perspectives
volume
120
issue
6
pages
879 - 884
publisher
National Institute of Environmental Health Science
external identifiers
  • wos:000304765700029
  • pmid:22382075
  • scopus:84862021998
ISSN
1552-9924
DOI
10.1289/ehp.1104600
language
English
LU publication?
yes
id
34795f21-4d6f-4c61-a37d-a2e6f28bac59 (old id 2432342)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22382075?dopt=Abstract
date added to LUP
2012-04-03 08:20:53
date last changed
2017-11-05 03:55:11
@article{34795f21-4d6f-4c61-a37d-a2e6f28bac59,
  abstract     = {Background: Cadmium, a common food pollutant, alters DNA methylation in vitro. Epigenetic effects might therefore partly explain cadmium's toxicity, including carcinogenicity, but human data on epigenetic effects are lacking. Objectives: To evaluate effects of dietary cadmium exposure on DNA methylation, considering other environmental exposures, genetic predisposition, and gene expression. <br/><br>
<br/><br>
Methods: Concentrations of cadmium, arsenic, selenium and zinc in blood and urine of nonsmoking women (N=202) from the Northern Argentinean Andes were measured by ICP-MS. Methylation in CpG islands of LINE1 (proxy for global DNA methylation) and promoter regions of p16 (CDKN2A) and MLH1 in peripheral blood were measured by bisulfite PCR pyrosequencing. Genotyping (N=172) for DNMT1 (rs10854076, rs2228611) and DNMT3B (rs2424913, rs2424932) was performed with SequenomTM; and gene expression (N=90) with DirectHyb HumanHT-12 v3.0. <br/><br>
<br/><br>
Results: Cadmium exposure was low: median concentrations in blood and urine were 0.36 and 0.23 µg/L, respectively. Urinary cadmium (ln transformed) was inversely associated with LINE1 methylation (β=-0.50, p=0.0070; β=-0.44, p=0.026 adjusted for age and coca chewing), but not with p16 or MLH1 methylation. Both DNMT1 rs10854076 and DNMT1 rs2228611 polymorphisms modified associations between urinary cadmium and LINE1 (p-values for interaction in adjusted models were 0.045 and 0.064, respectively). The rare genotypes demonstrated stronger hypomethylation with increasing urinary cadmium concentrations. Cadmium was inversely associated with DNMT3B (rs -0.28, p=0.0086), but not with DNMT1 expression (rs -0.075, p=0.48). <br/><br>
<br/><br>
Conclusion: Environmental cadmium exposure was associated with DNA hypomethylation in peripheral blood and DNMT1 genotypes modified this association. The role of epigenetic modifications in cadmium-associated diseases needs clarification.},
  author       = {Hossain, Mohammad Bakhtiar and Vahter, Marie and Concha, Gabriela and Broberg Palmgren, Karin},
  issn         = {1552-9924},
  language     = {eng},
  number       = {6},
  pages        = {879--884},
  publisher    = {National Institute of Environmental Health Science},
  series       = {Environmental Health Perspectives},
  title        = {Low-Level Environmental Cadmium Exposure is Associated with DNA Hypomethylation in Argentinean Women.},
  url          = {http://dx.doi.org/10.1289/ehp.1104600},
  volume       = {120},
  year         = {2012},
}