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ATP13A2 (PARK9) polymorphisms influence the neurotoxic effects of manganese.

Rentschler, Gerda LU ; Covolo, Loredana; Haddad, Amelia Ahmadi; Lucchini, Roberto G; Zoni, Silvia and Broberg Palmgren, Karin LU (2012) In NeuroToxicology 33(4). p.697-702
Abstract
INTRODUCTION: A higher prevalence of individuals affected by Parkinsonism was found in Valcamonica, Italy. This may be related to ferro-alloy smelters in the area, releasing manganese (Mn) in the air, soil and water for about a century. There exists individual susceptibility for Mn neurotoxicity. AIM: To analyse how polymorphism in genes regulating Mn metabolism and toxicity can modify neurophysiological effects of Mn exposure. MATERIALS AND METHODS: Elderly (N=255) and adolescents (N=311) from Northern Italy were examined for neuromotor and olfactory functions. Exposure to Mn was assessed in blood and urine by atomic absorption spectroscopy and in soil by a portable instrument based on X-Ray fluorescence technology. Polymorphisms in the... (More)
INTRODUCTION: A higher prevalence of individuals affected by Parkinsonism was found in Valcamonica, Italy. This may be related to ferro-alloy smelters in the area, releasing manganese (Mn) in the air, soil and water for about a century. There exists individual susceptibility for Mn neurotoxicity. AIM: To analyse how polymorphism in genes regulating Mn metabolism and toxicity can modify neurophysiological effects of Mn exposure. MATERIALS AND METHODS: Elderly (N=255) and adolescents (N=311) from Northern Italy were examined for neuromotor and olfactory functions. Exposure to Mn was assessed in blood and urine by atomic absorption spectroscopy and in soil by a portable instrument based on X-Ray fluorescence technology. Polymorphisms in the Parkinson-related gene ATPase type 13A2 (ATP13A2, also called PARK9: rs3738815, rs2076602, rs4920608, rs2871776 and rs2076600), and in the secretory pathway Ca(2+)/Mn(2+) ATPase isoform 1 gene (SPCA1: rs218498, rs3773814 and rs2669858) were analysed by TaqMan probes. RESULTS: For both adolescents and elderly, negative correlations between Mn in soil and motor coordination (R(s)=-0.20, p<0.001; R(s)=-0.13, p=0.05, respectively) were demonstrated. Also among adolescents, negative correlations were seen between Mn in soil with odor identification (R(s)=-0.17, p<0.01). No associations were seen for Mn in blood or urine. ATP13A2 polymorphisms rs4920608 and rs2871776 significantly modified the effects of Mn exposure on impaired motor coordination in elderly (p for interaction=0.029, p=0.041, respectively), also after adjustments for age and gender. The rs2871776 altered a binding site for transcription factor insulinoma-associated 1. CONCLUSIONS: ATP13A2 variation may be a risk marker for neurotoxic effects of Mn in humans. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
NeuroToxicology
volume
33
issue
4
pages
697 - 702
publisher
Elsevier
external identifiers
  • wos:000307617200012
  • pmid:22285144
  • scopus:84864497427
ISSN
1872-9711
DOI
10.1016/j.neuro.2012.01.007
language
English
LU publication?
yes
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0cf6df3e-5c60-465a-84e0-dd1313c05118 (old id 2335967)
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http://www.ncbi.nlm.nih.gov/pubmed/22285144?dopt=Abstract
date added to LUP
2012-02-01 23:11:13
date last changed
2017-09-10 04:08:46
@article{0cf6df3e-5c60-465a-84e0-dd1313c05118,
  abstract     = {INTRODUCTION: A higher prevalence of individuals affected by Parkinsonism was found in Valcamonica, Italy. This may be related to ferro-alloy smelters in the area, releasing manganese (Mn) in the air, soil and water for about a century. There exists individual susceptibility for Mn neurotoxicity. AIM: To analyse how polymorphism in genes regulating Mn metabolism and toxicity can modify neurophysiological effects of Mn exposure. MATERIALS AND METHODS: Elderly (N=255) and adolescents (N=311) from Northern Italy were examined for neuromotor and olfactory functions. Exposure to Mn was assessed in blood and urine by atomic absorption spectroscopy and in soil by a portable instrument based on X-Ray fluorescence technology. Polymorphisms in the Parkinson-related gene ATPase type 13A2 (ATP13A2, also called PARK9: rs3738815, rs2076602, rs4920608, rs2871776 and rs2076600), and in the secretory pathway Ca(2+)/Mn(2+) ATPase isoform 1 gene (SPCA1: rs218498, rs3773814 and rs2669858) were analysed by TaqMan probes. RESULTS: For both adolescents and elderly, negative correlations between Mn in soil and motor coordination (R(s)=-0.20, p&lt;0.001; R(s)=-0.13, p=0.05, respectively) were demonstrated. Also among adolescents, negative correlations were seen between Mn in soil with odor identification (R(s)=-0.17, p&lt;0.01). No associations were seen for Mn in blood or urine. ATP13A2 polymorphisms rs4920608 and rs2871776 significantly modified the effects of Mn exposure on impaired motor coordination in elderly (p for interaction=0.029, p=0.041, respectively), also after adjustments for age and gender. The rs2871776 altered a binding site for transcription factor insulinoma-associated 1. CONCLUSIONS: ATP13A2 variation may be a risk marker for neurotoxic effects of Mn in humans.},
  author       = {Rentschler, Gerda and Covolo, Loredana and Haddad, Amelia Ahmadi and Lucchini, Roberto G and Zoni, Silvia and Broberg Palmgren, Karin},
  issn         = {1872-9711},
  language     = {eng},
  number       = {4},
  pages        = {697--702},
  publisher    = {Elsevier},
  series       = {NeuroToxicology},
  title        = {ATP13A2 (PARK9) polymorphisms influence the neurotoxic effects of manganese.},
  url          = {http://dx.doi.org/10.1016/j.neuro.2012.01.007},
  volume       = {33},
  year         = {2012},
}