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Polymorphisms in Ma...
Polymorphisms in Manganese Transporters SLC30A10 and SLC39A8 Are Associated With Children's Neurodevelopment by Influencing Manganese Homeostasis
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- Wahlberg, Karin E (author)
- Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine
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- Guazzetti, Stefano (author)
- Azienda USL-IRCCS di Reggio Emilia
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- Pineda, Daniela (author)
- Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine
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- Larsson, Susanna C. (author)
- Karolinska Institute,Karolinska Institutet,Uppsala universitet,Ortopedi
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- Fedrighi, Chiara (author)
- University of Brescia
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- Cagna, Giuseppa (author)
- University of Brescia
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- Zoni, Silvia (author)
- University of Brescia
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- Placidi, Donatella (author)
- University of Brescia
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- Wright, Robert O (author)
- Icahn School of Medicine at Mount Sinai
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- Smith, Donald R (author)
- University of California, Santa Cruz
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- Lucchini, Roberto G (author)
- Icahn School of Medicine at Mount Sinai
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- Broberg, Karin (author)
- Karolinska Institute,Lund University,Lunds universitet,Karolinska Institutet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine
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(creator_code:org_t)
- 2018-12-20
- 2018
- English.
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In: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 9
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Abstract
Subject headings
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- Background: Manganese (Mn) is an essential element but at excessive levels, it is neurotoxic. Even a moderate increase in Mn has been suggested to interfere with neurodevelopment in children. Genetics influencing Mn concentrations and toxicity is unclear. Objective: We assessed, in a cross-sectional study, whether common single-nucleotide polymorphisms in the Mn transporters SLC39A8 (influx) and SLC30A10 (efflux) are associated with neurodevelopment in children. Design: We genotyped SLC39A8 (rs13107325 C/T) and SLC30A10 (rs1776029 G/A and rs12064812 T/C) in Italian children (n = 686, ages 11-14). We then used linear regression models to analyze associations between genotype, blood Mn concentrations, and neurodevelopmental outcomes including intelligence, behavior, motor function, and sway. Inferred causal relationships were evaluated using instrumental variables (IV) analysis. Results: For SLC30A10 rs1776029, the minor allele (A) was associated with increased average blood Mn of 41% (p < 0.001), whereas minor alleles for rs12064812 (C) and rs13107325 (T) were associated with reduced blood Mn of 7% (p = 0.002) and 15% (p < 0.001), respectively. For children carrying genotypes associated with high blood Mn, we observed lower performance for certain IQ subtests, increased sway, and increased scores for behavioral problems. High Mn genotypes showed odds ratios of 2-4 (p ≤ 0.01) for high scores in tests assessing ADHD-related behavior. IV analyses suggested that several of the associations were mediated by blood Mn. Conclusions: Our results suggest that common polymorphisms in SLC39A8 and SLC30A10 influence neurodevelopmental outcomes in children via differences in Mn homeostasis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Annan medicin och hälsovetenskap -- Övrig annan medicin och hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Other Medical and Health Sciences -- Other Medical and Health Sciences not elsewhere specified (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- ADHD
- SLC30A10
- SLC39A8
- manganese
- neurodevelopment
- neurotoxicity
Publication and Content Type
- ref (subject category)
- art (subject category)
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Wahlberg, Karin ...
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Guazzetti, Stefa ...
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Pineda, Daniela
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Larsson, Susanna ...
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Fedrighi, Chiara
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Cagna, Giuseppa
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Zoni, Silvia
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Placidi, Donatel ...
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Wright, Robert O
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Smith, Donald R
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Lucchini, Robert ...
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Broberg, Karin
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Other Medical an ...
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and Other Medical an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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Frontiers in Gen ...
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Uppsala University
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Karolinska Institutet
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Lund University