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Arsenic exposure in early pregnancy alters genome-wide DNA methylation in cord blood, particularly in boys.

Broberg, K; Salih, A; Engström, Karin LU ; Hossain, M B; Jurkovic Mlakar, S; Bottai, M; Grandér, M; Raqib, R and Vahter, M (2014) In Journal of Developmental Origins of Health and Disease 5(4). p.288-298
Abstract
Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium... (More)
Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov-Smirnov test, P-value<10-15), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (r S -values>-0.62), but in girls only 207 (41%) showed inverse correlation (r S -values>-0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Developmental Origins of Health and Disease
volume
5
issue
4
pages
288 - 298
publisher
Cambridge University Press
external identifiers
  • pmid:24965135
  • wos:000337758200003
  • scopus:84903271988
ISSN
2040-1752
DOI
10.1017/S2040174414000221
language
English
LU publication?
yes
id
f4840111-17ff-4e89-8f45-c055f46125d8 (old id 4526801)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24965135?dopt=Abstract
date added to LUP
2014-07-07 21:03:50
date last changed
2017-11-12 03:03:03
@article{f4840111-17ff-4e89-8f45-c055f46125d8,
  abstract     = {Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov-Smirnov test, P-value&lt;10-15), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (r S -values&gt;-0.62), but in girls only 207 (41%) showed inverse correlation (r S -values&gt;-0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.},
  author       = {Broberg, K and Salih, A and Engström, Karin and Hossain, M B and Jurkovic Mlakar, S and Bottai, M and Grandér, M and Raqib, R and Vahter, M},
  issn         = {2040-1752},
  language     = {eng},
  number       = {4},
  pages        = {288--298},
  publisher    = {Cambridge University Press},
  series       = {Journal of Developmental Origins of Health and Disease},
  title        = {Arsenic exposure in early pregnancy alters genome-wide DNA methylation in cord blood, particularly in boys.},
  url          = {http://dx.doi.org/10.1017/S2040174414000221},
  volume       = {5},
  year         = {2014},
}