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Prenatal arsenic ex...
Prenatal arsenic exposure is associated with increased plasma IGFBP3 concentrations in 9-year-old children partly via changes in DNA methylation
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- Gliga, Anda R (författare)
- Karolinska Institutet,Karolinska Institute,International Centre for Diarrhoeal Disease Research, Bangladesh
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- Engström, Karin (författare)
- Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Miljöepidemiologi,Forskargrupper vid Lunds universitet,EPI@LUND,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine,Environmental Epidemiology,Lund University Research Groups
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- Kippler, Maria (författare)
- Karolinska Institutet,Karolinska Institute
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- Skröder, Helena (författare)
- Karolinska Institutet,Karolinska Institute
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- Ahmed, Sultan (författare)
- International Centre for Diarrhoeal Disease Research, Bangladesh
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- Vahter, Marie (författare)
- Karolinska Institutet,Karolinska Institute
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- Raqib, Rubhana (författare)
- International Centre for Diarrhoeal Disease Research, Bangladesh
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- Broberg, Karin (författare)
- Karolinska Institutet,Karolinska Institute
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(creator_code:org_t)
- 2018-06-08
- 2018
- Engelska.
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 92:8, s. 2487-2500
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Exposure to inorganic arsenic (As), a carcinogen and epigenetic toxicant, has been associated with lower circulating levels of insulin-like growth factor 1 (IGF1) and impaired growth in children of pre-school age. The aim of this study was to assess the potential impact of exposure to As on IGF1 and insulin-like growth factor-binding protein 3 (IGFBP3) as well as DNA methylation changes in 9-year-old children. To this end, we studied 9-year-old children from a longitudinal mother-child cohort in rural Bangladesh (n = 551). Prenatal and concurrent exposure to As was assessed via concentrations in maternal urine at gestational week 8 and in child urine at 9 years, measured by HPLC-HG-ICPMS. Plasma IGF1 and IGFBP3 concentrations were quantified with immunoassays. DNA methylation was measured in blood mononuclear cells at 9 years in a sub-sample (n = 113) using the Infinium HumanMethylation450K BeadChip. In multivariable-adjusted linear regression models, prenatal As (natural log-transformed), but not children's concurrent urinary As, was positively associated with IGFBP3 concentrations (β = 76, 95% CI 19, 133). As concentrations were not associated with IGF1. DNA methylation analysis revealed CpGs associated with both prenatal As and IGFBP3. Mediation analysis suggested that methylation of 12 CpG sites for all children was mediator of effect for the association between prenatal As and IGFBP3. We also found differentially methylated regions, generally hypermethylated, that were associated with both prenatal As and IGFBP3. In all, our study revealed that prenatal exposure to As was positively associated with IGFBP3 concentrations in children at 9 years, independent of IGF1, and this association may, at least in part, be epigenetically mediated.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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