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Polymorphisms in manganese transporters show developmental stage and sex specific associations with manganese concentrations in primary teeth

Wahlberg, Karin LU ; Arora, Manish; Curtin, Austen; Curtin, Paul; Wright, Robert O.; Smith, Donald R; Lucchini, Roberto G.; Broberg, Karin LU and Austin, Christine (2017) In NeuroToxicology
Abstract

Background: Manganese (Mn) is an essential metal that can become neurotoxic at elevated levels with negative consequences on neurodevelopment. We have evaluated the influence of single nucleotide polymorphisms (SNPs) in Mn transporter genes SLC30A10 and SLC39A8 on Mn concentrations in dentine, a validated biomarker that reflects Mn tissue concentrations early in life. Methods: The study included 195 children with variable environmental Mn exposure. Mn concentrations in dentine representing fetal, early postnatal and early childhood developmental periods were measured using laser ablation-inductively coupled plasma mass spectrometry. SLC30A10 rs12064812 (T/C) and SLC39A8 rs13107325 (C/T) were genotyped by TaqMan real time PCR and... (More)

Background: Manganese (Mn) is an essential metal that can become neurotoxic at elevated levels with negative consequences on neurodevelopment. We have evaluated the influence of single nucleotide polymorphisms (SNPs) in Mn transporter genes SLC30A10 and SLC39A8 on Mn concentrations in dentine, a validated biomarker that reflects Mn tissue concentrations early in life. Methods: The study included 195 children with variable environmental Mn exposure. Mn concentrations in dentine representing fetal, early postnatal and early childhood developmental periods were measured using laser ablation-inductively coupled plasma mass spectrometry. SLC30A10 rs12064812 (T/C) and SLC39A8 rs13107325 (C/T) were genotyped by TaqMan real time PCR and SLC30A10 rs1776029 (G/A) by pyrosequencing; and SNPs were analyzed in association with Mn in dentine. Results: SLC39A8 rs13107325 rare allele (T) carriers had significantly higher Mn concentrations in postnatal dentine (110%, p = 0.008). For all SNPs we also observed non-significant associations with Mn concentrations in dentine in opposite directions for fetal and early postnatal periods. Furthermore, there were significant differences in the influence of SLC30A10 rs1776929 genotypes on Mn concentrations in dentine between sexes. Discussion: The findings from this study indicate that common SNPs in Mn transporters influence Mn homeostasis in early development and may therefore be important to consider in future studies of early life Mn exposure and health effects. Our results also suggest that the influence of these transporters on Mn regulation may differ by developmental stage, as well as between girls and boys.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Manganese homeostasis, Manganese neurotoxicity, Manganese transporter genetics, SLC30A10, SLC39A8, Teeth biomarkers
in
NeuroToxicology
publisher
Elsevier
external identifiers
  • scopus:85029499660
ISSN
0161-813X
DOI
10.1016/j.neuro.2017.09.003
language
English
LU publication?
yes
id
58a9a3e9-9e38-4500-8694-a9f0f6e01b10
date added to LUP
2017-10-05 08:40:22
date last changed
2018-01-07 12:20:41
@article{58a9a3e9-9e38-4500-8694-a9f0f6e01b10,
  abstract     = {<p>Background: Manganese (Mn) is an essential metal that can become neurotoxic at elevated levels with negative consequences on neurodevelopment. We have evaluated the influence of single nucleotide polymorphisms (SNPs) in Mn transporter genes SLC30A10 and SLC39A8 on Mn concentrations in dentine, a validated biomarker that reflects Mn tissue concentrations early in life. Methods: The study included 195 children with variable environmental Mn exposure. Mn concentrations in dentine representing fetal, early postnatal and early childhood developmental periods were measured using laser ablation-inductively coupled plasma mass spectrometry. SLC30A10 rs12064812 (T/C) and SLC39A8 rs13107325 (C/T) were genotyped by TaqMan real time PCR and SLC30A10 rs1776029 (G/A) by pyrosequencing; and SNPs were analyzed in association with Mn in dentine. Results: SLC39A8 rs13107325 rare allele (T) carriers had significantly higher Mn concentrations in postnatal dentine (110%, p = 0.008). For all SNPs we also observed non-significant associations with Mn concentrations in dentine in opposite directions for fetal and early postnatal periods. Furthermore, there were significant differences in the influence of SLC30A10 rs1776929 genotypes on Mn concentrations in dentine between sexes. Discussion: The findings from this study indicate that common SNPs in Mn transporters influence Mn homeostasis in early development and may therefore be important to consider in future studies of early life Mn exposure and health effects. Our results also suggest that the influence of these transporters on Mn regulation may differ by developmental stage, as well as between girls and boys.</p>},
  author       = {Wahlberg, Karin and Arora, Manish and Curtin, Austen and Curtin, Paul and Wright, Robert O. and Smith, Donald R and Lucchini, Roberto G. and Broberg, Karin and Austin, Christine},
  issn         = {0161-813X},
  keyword      = {Manganese homeostasis,Manganese neurotoxicity,Manganese transporter genetics,SLC30A10,SLC39A8,Teeth biomarkers},
  language     = {eng},
  month        = {09},
  publisher    = {Elsevier},
  series       = {NeuroToxicology},
  title        = {Polymorphisms in manganese transporters show developmental stage and sex specific associations with manganese concentrations in primary teeth},
  url          = {http://dx.doi.org/10.1016/j.neuro.2017.09.003},
  year         = {2017},
}