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Genetics and Epigenetics of Manganese Toxicity

Lindner, Sabrina LU ; Lucchini, Roberto and Broberg, Karin LU orcid (2022) In Current Environmental Health Reports 9(4). p.697-713
Abstract

Purpose of Review: At elevated levels, the essential element manganese (Mn) is neurotoxic and increasing evidence indicates that environmental Mn exposure early in life negatively affects neurodevelopment. In this review, we describe how underlying genetics may confer susceptibility to elevated Mn concentrations and how the epigenetic effects of Mn may explain the association between Mn exposure early in life and its toxic effects later in life. Recent Findings: Common polymorphisms in the Mn transporter genes SLC30A10 and SLC39A8 seem to have a large impact on intracellular Mn levels and, in turn, neurotoxicity. Genetic variation in iron regulatory genes may to lesser extent also influence Mn levels and toxicity. Recent studies on Mn... (More)

Purpose of Review: At elevated levels, the essential element manganese (Mn) is neurotoxic and increasing evidence indicates that environmental Mn exposure early in life negatively affects neurodevelopment. In this review, we describe how underlying genetics may confer susceptibility to elevated Mn concentrations and how the epigenetic effects of Mn may explain the association between Mn exposure early in life and its toxic effects later in life. Recent Findings: Common polymorphisms in the Mn transporter genes SLC30A10 and SLC39A8 seem to have a large impact on intracellular Mn levels and, in turn, neurotoxicity. Genetic variation in iron regulatory genes may to lesser extent also influence Mn levels and toxicity. Recent studies on Mn and epigenetic mechanisms indicate that Mn-related changes in DNA methylation occur early in life. One human and two animal studies found persistent changes from in utero exposure to Mn but whether these changes have functional effects remains unknown. Summary: Genetics seems to play a major role in susceptibility to Mn toxicity and should therefore be considered in risk assessment. Mn appears to interfere with epigenetic processes, potentially leading to persistent changes in developmental programming, which warrants further study.

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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
DNA methylation, HFE, Manganese, SLC30A10, SLC39A8
in
Current Environmental Health Reports
volume
9
issue
4
pages
17 pages
publisher
Springer
external identifiers
  • scopus:85141719785
  • pmid:36357556
ISSN
2196-5412
DOI
10.1007/s40572-022-00384-2
language
English
LU publication?
yes
id
c650ef8a-1a04-44ad-adbf-954f1c67d708
date added to LUP
2022-12-05 14:59:24
date last changed
2024-06-13 21:07:26
@article{c650ef8a-1a04-44ad-adbf-954f1c67d708,
  abstract     = {{<p>Purpose of Review: At elevated levels, the essential element manganese (Mn) is neurotoxic and increasing evidence indicates that environmental Mn exposure early in life negatively affects neurodevelopment. In this review, we describe how underlying genetics may confer susceptibility to elevated Mn concentrations and how the epigenetic effects of Mn may explain the association between Mn exposure early in life and its toxic effects later in life. Recent Findings: Common polymorphisms in the Mn transporter genes SLC30A10 and SLC39A8 seem to have a large impact on intracellular Mn levels and, in turn, neurotoxicity. Genetic variation in iron regulatory genes may to lesser extent also influence Mn levels and toxicity. Recent studies on Mn and epigenetic mechanisms indicate that Mn-related changes in DNA methylation occur early in life. One human and two animal studies found persistent changes from in utero exposure to Mn but whether these changes have functional effects remains unknown. Summary: Genetics seems to play a major role in susceptibility to Mn toxicity and should therefore be considered in risk assessment. Mn appears to interfere with epigenetic processes, potentially leading to persistent changes in developmental programming, which warrants further study.</p>}},
  author       = {{Lindner, Sabrina and Lucchini, Roberto and Broberg, Karin}},
  issn         = {{2196-5412}},
  keywords     = {{DNA methylation; HFE; Manganese; SLC30A10; SLC39A8}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{697--713}},
  publisher    = {{Springer}},
  series       = {{Current Environmental Health Reports}},
  title        = {{Genetics and Epigenetics of Manganese Toxicity}},
  url          = {{http://dx.doi.org/10.1007/s40572-022-00384-2}},
  doi          = {{10.1007/s40572-022-00384-2}},
  volume       = {{9}},
  year         = {{2022}},
}