ATP13A2 (PARK9) polymorphisms influence the neurotoxic effects of manganese.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2335967
- author
- Rentschler, Gerda LU ; Covolo, Loredana ; Haddad, Amelia Ahmadi ; Lucchini, Roberto G ; Zoni, Silvia and Broberg Palmgren, Karin LU
- organization
- publishing date
- 2012
- 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
- pmid:22285144
- ISSN
- 1872-9711
- DOI
- 10.1016/j.neuro.2012.01.007
- language
- English
- LU publication?
- yes
- id
- 0cf6df3e-5c60-465a-84e0-dd1313c05118 (old id 2335967)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22285144?dopt=Abstract
- date added to LUP
- 2016-04-01 13:56:57
- date last changed
- 2022-03-29 18:17:25
@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<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.}}, 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 = {{https://lup.lub.lu.se/search/files/3681011/2374457.pdf}}, doi = {{10.1016/j.neuro.2012.01.007}}, volume = {{33}}, year = {{2012}}, }