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Metal Exposure and SNCA rs356219 Polymorphism Associated With Parkinson Disease and Parkinsonism

Lucchini, Roberto G. ; Guazzetti, Stefano ; Renzetti, Stefano ; Broberg, Karin LU orcid ; Caci, Margherita ; Covolo, Loredana ; Crippa, Patrizia ; Gelatti, Umberto ; Hashim, Dana and Oppini, Manuela , et al. (2020) In Frontiers in Neurology 11.
Abstract

Objective: In the province of Brescia, Italy, historical neurotoxic metal exposure has occurred for several decades. This study aimed to explore the role of metal exposure and genetics on Parkinson's Disease (PD) and Parkinsonism. Methods: Cases were enrolled from four local clinics for movement disorders. Randomly selected controls non-affected by neurological or psychiatric conditions were enrolled from the same health centers keeping a similar gender ratio and age distribution as for cases. Data on sociodemographic variables, clinical onset and life habits were collected besides accurate occupational and residential history. Blood samples were collected from all participants for genotyping of target polymorphisms in genes linked to... (More)

Objective: In the province of Brescia, Italy, historical neurotoxic metal exposure has occurred for several decades. This study aimed to explore the role of metal exposure and genetics on Parkinson's Disease (PD) and Parkinsonism. Methods: Cases were enrolled from four local clinics for movement disorders. Randomly selected controls non-affected by neurological or psychiatric conditions were enrolled from the same health centers keeping a similar gender ratio and age distribution as for cases. Data on sociodemographic variables, clinical onset and life habits were collected besides accurate occupational and residential history. Blood samples were collected from all participants for genotyping of target polymorphisms in genes linked to PD and/or metal transport. Results: A total number of 432 cases and 444 controls were enrolled in the study, with average age of 71 years (72.2 for cases and 70 for controls). The average age at diagnosis was 65.9 years (SD 9.9). Among the potential risk factors, family history of PD or Parkinsonism showed the strongest association with the diseases (OR = 4.2, 95% CI 2.3, 7.6 on PD; OR = 4.3, 95% CI 1.9, 9.5 for Parkinsonism), followed by polymorphism rs356219 in the alpha-synuclein (SNCA) gene (OR = 2.03, 95% CI 1.3, 3.3 for CC vs. TT on PD; OR = 2.5, 95% CI 1.1, 5.3 for CC vs. TT on Parkinsonism), exposure to metals (OR = 2.4;, 95% CI 1.3, 4.2 on PD), being born in a farm (OR = 1.8; 95% CI 1.1, 2.8 on PD; OR = 2.6; 95% CI 1.4, 4.9 on Parkinsonism) and being born in the province of Brescia (OR = 1.7; 95% CI 1.0, 2.9 on PD). Conditional OR of having PD depending by SNCA polymorphism and metal exposure highlights higher risk of PD among CC SNCA carriers and being exposed to metals. However, the interaction term was not statistically significant. Conclusions: Lifetime exposure to metals and genetic variation in SNCA gene are relevant determinants of PD and Parkinsonism in the highly industrialized area of Brescia, Italy. The lack of evidence of statistical interaction between environmental and genetic factors may be due to the low frequencies of subjects representing the exposure categories and the polymorphism variants and does not rule out the biological interaction.

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Contribution to journal
publication status
published
subject
keywords
manganese, metal exposure, occupational exposure, parkinson disease, parkinsonism, SNCA gene
in
Frontiers in Neurology
volume
11
article number
556337
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85098062988
  • pmid:33362685
ISSN
1664-2295
DOI
10.3389/fneur.2020.556337
language
English
LU publication?
yes
id
ea3a710f-d73b-485f-bde6-229c985e00f4
date added to LUP
2021-01-05 13:35:51
date last changed
2024-02-17 10:52:34
@article{ea3a710f-d73b-485f-bde6-229c985e00f4,
  abstract     = {{<p>Objective: In the province of Brescia, Italy, historical neurotoxic metal exposure has occurred for several decades. This study aimed to explore the role of metal exposure and genetics on Parkinson's Disease (PD) and Parkinsonism. Methods: Cases were enrolled from four local clinics for movement disorders. Randomly selected controls non-affected by neurological or psychiatric conditions were enrolled from the same health centers keeping a similar gender ratio and age distribution as for cases. Data on sociodemographic variables, clinical onset and life habits were collected besides accurate occupational and residential history. Blood samples were collected from all participants for genotyping of target polymorphisms in genes linked to PD and/or metal transport. Results: A total number of 432 cases and 444 controls were enrolled in the study, with average age of 71 years (72.2 for cases and 70 for controls). The average age at diagnosis was 65.9 years (SD 9.9). Among the potential risk factors, family history of PD or Parkinsonism showed the strongest association with the diseases (OR = 4.2, 95% CI 2.3, 7.6 on PD; OR = 4.3, 95% CI 1.9, 9.5 for Parkinsonism), followed by polymorphism rs356219 in the alpha-synuclein (SNCA) gene (OR = 2.03, 95% CI 1.3, 3.3 for CC vs. TT on PD; OR = 2.5, 95% CI 1.1, 5.3 for CC vs. TT on Parkinsonism), exposure to metals (OR = 2.4;, 95% CI 1.3, 4.2 on PD), being born in a farm (OR = 1.8; 95% CI 1.1, 2.8 on PD; OR = 2.6; 95% CI 1.4, 4.9 on Parkinsonism) and being born in the province of Brescia (OR = 1.7; 95% CI 1.0, 2.9 on PD). Conditional OR of having PD depending by SNCA polymorphism and metal exposure highlights higher risk of PD among CC SNCA carriers and being exposed to metals. However, the interaction term was not statistically significant. Conclusions: Lifetime exposure to metals and genetic variation in SNCA gene are relevant determinants of PD and Parkinsonism in the highly industrialized area of Brescia, Italy. The lack of evidence of statistical interaction between environmental and genetic factors may be due to the low frequencies of subjects representing the exposure categories and the polymorphism variants and does not rule out the biological interaction.</p>}},
  author       = {{Lucchini, Roberto G. and Guazzetti, Stefano and Renzetti, Stefano and Broberg, Karin and Caci, Margherita and Covolo, Loredana and Crippa, Patrizia and Gelatti, Umberto and Hashim, Dana and Oppini, Manuela and Pepe, Fulvio and Pilotto, Andrea and Passeri, Chiara and Placidi, Donatella and Rizzetti, Maira Cristina and Turla, Marinella and Wahlberg, Karin and Padovani, Alessandro}},
  issn         = {{1664-2295}},
  keywords     = {{manganese; metal exposure; occupational exposure; parkinson disease; parkinsonism; SNCA gene}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Neurology}},
  title        = {{Metal Exposure and SNCA rs356219 Polymorphism Associated With Parkinson Disease and Parkinsonism}},
  url          = {{http://dx.doi.org/10.3389/fneur.2020.556337}},
  doi          = {{10.3389/fneur.2020.556337}},
  volume       = {{11}},
  year         = {{2020}},
}