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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2432342
- author
- Hossain, Mohammad Bakhtiar
; Vahter, Marie
; Concha, Gabriela
and Broberg Palmgren, Karin
LU
- organization
- publishing date
- 2012
- 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 Sciences
- external identifiers
-
- wos:000304765700029
- pmid:22382075
- scopus:84862021998
- pmid:22382075
- 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
- 2016-04-01 13:16:08
- date last changed
- 2022-04-21 20:40:56
@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 Sciences}},
series = {{Environmental Health Perspectives}},
title = {{Low-Level Environmental Cadmium Exposure is Associated with DNA Hypomethylation in Argentinean Women.}},
url = {{https://lup.lub.lu.se/search/files/3268560/2856871.pdf}},
doi = {{10.1289/ehp.1104600}},
volume = {{120}},
year = {{2012}},
}