ATP13A2 (PARK9) polymorphisms influence the neurotoxic effects of manganese.
Neurotoxicology
; 33(4): 697-702, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-22285144
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 ANDMETHODS:
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson Secundária
/
Poluentes do Solo
/
ATPases Translocadoras de Prótons
/
Intoxicação por Manganês
/
Exposição Ambiental
/
Ferro
/
Manganês
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged80
País/Região como assunto:
Europa
Idioma:
En
Revista:
Neurotoxicology
Ano de publicação:
2012
Tipo de documento:
Article