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Common polymorphisms in the solute carrier SLC30A10 are associated with blood manganese and neurological function.

Wahlberg, Karin E LU ; Kippler, Maria; Alhamdow, Ayman LU ; Rahman, Syed Moshfiqur; Smith, Donald R; Vahter, Marie; Lucchini, Roberto and Broberg Palmgren, Karin LU (2015) In Toxicological Sciences 149(2). p.473-483
Abstract
Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes a Mn transporter, influence blood Mn concentrations and neurological function. We measured blood Mn concentrations by ICP-MS or atomic absorption spectroscopy and genotyped two SLC30A10 non-coding SNPs (rs2275707 and rs12064812) by TaqMan PCR in cohorts from Bangladesh (N=406), the Argentinean Andes (N=198), and Italy (N=238). We also measured SLC30A10 expression in whole blood by TaqMan PCR in a sub-group (N=101) from the Andean cohort, and... (More)
Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes a Mn transporter, influence blood Mn concentrations and neurological function. We measured blood Mn concentrations by ICP-MS or atomic absorption spectroscopy and genotyped two SLC30A10 non-coding SNPs (rs2275707 and rs12064812) by TaqMan PCR in cohorts from Bangladesh (N=406), the Argentinean Andes (N=198), and Italy (N=238). We also measured SLC30A10 expression in whole blood by TaqMan PCR in a sub-group (N=101) from the Andean cohort, and neurological parameters (sway velocity and finger-tapping speed) in the Italian cohort.The rs2275707 variant allele was associated with increased Mn concentrations in the Andes (8%, p=0.027) and Italy (10.6%, p=0.012), but not as clear in Bangladesh (3.4%, p=0.21; linear regression analysis adjusted for age, gender, and plasma ferritin). This allele was also associated with increased sway velocity (15%, p=0.033; adjusted for age and sex) and reduced SLC30A10 expression (-24.6%, p=0.029). By contrast, the rs12064812 variant homozygous genotype was associated with reduced Mn concentrations, particularly in the Italian cohort (-18.4%, p=0.04), and increased finger-tapping speed (8.7%, p=0.025).We show that common SNPs in SLC30A10 are associated with blood Mn concentrations in three unrelated cohorts and that their influence may be mediated by altered SLC30A10 expression. Moreover, the SNPs appeared to influence neurological functions independent of blood Mn concentrations, suggesting that SLC30A10 could regulate brain Mn levels. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Toxicological Sciences
volume
149
issue
2
pages
473 - 483
publisher
Oxford University Press
external identifiers
  • PMID:26628504
  • Scopus:84960097435
  • WOS:000371613900020
ISSN
1096-0929
DOI
10.1093/toxsci/kfv252
language
English
LU publication?
yes
id
05e26ac2-8394-4d97-b3ec-bf7236871d4f (old id 8505849)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26628504?dopt=Abstract
date added to LUP
2016-01-04 20:31:09
date last changed
2016-10-25 08:41:36
@misc{05e26ac2-8394-4d97-b3ec-bf7236871d4f,
  abstract     = {Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes a Mn transporter, influence blood Mn concentrations and neurological function. We measured blood Mn concentrations by ICP-MS or atomic absorption spectroscopy and genotyped two SLC30A10 non-coding SNPs (rs2275707 and rs12064812) by TaqMan PCR in cohorts from Bangladesh (N=406), the Argentinean Andes (N=198), and Italy (N=238). We also measured SLC30A10 expression in whole blood by TaqMan PCR in a sub-group (N=101) from the Andean cohort, and neurological parameters (sway velocity and finger-tapping speed) in the Italian cohort.The rs2275707 variant allele was associated with increased Mn concentrations in the Andes (8%, p=0.027) and Italy (10.6%, p=0.012), but not as clear in Bangladesh (3.4%, p=0.21; linear regression analysis adjusted for age, gender, and plasma ferritin). This allele was also associated with increased sway velocity (15%, p=0.033; adjusted for age and sex) and reduced SLC30A10 expression (-24.6%, p=0.029). By contrast, the rs12064812 variant homozygous genotype was associated with reduced Mn concentrations, particularly in the Italian cohort (-18.4%, p=0.04), and increased finger-tapping speed (8.7%, p=0.025).We show that common SNPs in SLC30A10 are associated with blood Mn concentrations in three unrelated cohorts and that their influence may be mediated by altered SLC30A10 expression. Moreover, the SNPs appeared to influence neurological functions independent of blood Mn concentrations, suggesting that SLC30A10 could regulate brain Mn levels.},
  author       = {Wahlberg, Karin E and Kippler, Maria and Alhamdow, Ayman and Rahman, Syed Moshfiqur and Smith, Donald R and Vahter, Marie and Lucchini, Roberto and Broberg Palmgren, Karin},
  issn         = {1096-0929},
  language     = {eng},
  month        = {12},
  number       = {2},
  pages        = {473--483},
  publisher    = {ARRAY(0xa3ea288)},
  series       = {Toxicological Sciences},
  title        = {Common polymorphisms in the solute carrier SLC30A10 are associated with blood manganese and neurological function.},
  url          = {http://dx.doi.org/10.1093/toxsci/kfv252},
  volume       = {149},
  year         = {2015},
}