TY - JOUR
T1 - ATP13A2 (PARK9) polymorphisms influence the neurotoxic effects of manganese
AU - Rentschler, Gerda
AU - Covolo, Loredana
AU - Ahmadi Haddad, Amelia
AU - Lucchini, Roberto G.
AU - Zoni, Silvia
AU - Broberg, Karin
N1 - Funding Information:
The authors would like to thank Mrs. Karin Paulsson for help with genotyping. This study was supported by funding from the European Union through its Sixth Framework Programme for RTD (contract no FOOD-CT-2006-016253). It reflects only the authors’ views, and the European Commission is not liable for any use that may be made of the information contained therein. The project described was supported also by Award Number R01ES019222 from the National Institute Of Environmental Health Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Of Environmental Health Sciences or the National Institutes of Health.
PY - 2012/8
Y1 - 2012/8
N2 - 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 Ca2+/Mn2+ 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 (Rs=-0.20, p<0.001; Rs=-0.13, p=0.05, respectively) were demonstrated. Also among adolescents, negative correlations were seen between Mn in soil with odor identification (Rs=-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.
AB - 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 Ca2+/Mn2+ 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 (Rs=-0.20, p<0.001; Rs=-0.13, p=0.05, respectively) were demonstrated. Also among adolescents, negative correlations were seen between Mn in soil with odor identification (Rs=-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.
KW - Ferro-manganese
KW - Gene-environment
KW - Motor
KW - Neurophysiological
KW - Odor
KW - Parkinson
KW - SPCA1
KW - Tremor
UR - http://www.scopus.com/inward/record.url?scp=84864497427&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2012.01.007
DO - 10.1016/j.neuro.2012.01.007
M3 - Article
C2 - 22285144
AN - SCOPUS:84864497427
SN - 0161-813X
VL - 33
SP - 697
EP - 702
JO - NeuroToxicology
JF - NeuroToxicology
IS - 4
ER -