Gene-environment interactions in parkinsonism and Parkinson's disease

The Geoparkinson study

Finlay David Dick, G. De Palma, A. Ahmadi, Aileen Osborne, Neil William Scott, Gordon James Prescott, Jill Bennett, Sean Semple, Smita Dick, P. Mozzoni, Neva Elizabeth Haites, S. Bezzina Wettinger, A. Mutti, M. Otelea, Anthony Seaton, P. Soderkvist, A. Felice, Geoparkinson Study Group

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

OBJECTIVES: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. RESULTS: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). CONCLUSIONS: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.
Original languageEnglish
Pages (from-to)673-680
Number of pages8
JournalOccupational and Environmental Medicine
Volume64
Issue number10
Early online date20 Apr 2007
DOIs
Publication statusPublished - Oct 2007

Fingerprint

Gene-Environment Interaction
Parkinsonian Disorders
Parkinson Disease
Monoamine Oxidase
Genes
Cytochrome P-450 CYP2D6
Inborn Genetic Diseases
Genetic Polymorphisms
Manganese
Pesticides
Case-Control Studies
Copper
Dopamine
Iron
Logistic Models
Metals
Genotype

Keywords

  • case-control studies
  • environmental exposure
  • Europe
  • female
  • genetic predisposition to disease
  • genotype
  • humans
  • male
  • odds ratio
  • Parkinson Disease
  • polymorphism, genetic
  • risk factors
  • sex distribution

Cite this

Gene-environment interactions in parkinsonism and Parkinson's disease : The Geoparkinson study. / Dick, Finlay David; De Palma, G.; Ahmadi, A.; Osborne, Aileen; Scott, Neil William; Prescott, Gordon James; Bennett, Jill; Semple, Sean; Dick, Smita; Mozzoni, P.; Haites, Neva Elizabeth; Wettinger, S. Bezzina; Mutti, A.; Otelea, M.; Seaton, Anthony; Soderkvist, P.; Felice, A.; Geoparkinson Study Group.

In: Occupational and Environmental Medicine, Vol. 64, No. 10, 10.2007, p. 673-680.

Research output: Contribution to journalArticle

Dick, FD, De Palma, G, Ahmadi, A, Osborne, A, Scott, NW, Prescott, GJ, Bennett, J, Semple, S, Dick, S, Mozzoni, P, Haites, NE, Wettinger, SB, Mutti, A, Otelea, M, Seaton, A, Soderkvist, P, Felice, A & Geoparkinson Study Group 2007, 'Gene-environment interactions in parkinsonism and Parkinson's disease: The Geoparkinson study', Occupational and Environmental Medicine, vol. 64, no. 10, pp. 673-680. https://doi.org/10.1136/oem.2006.032078
Dick, Finlay David ; De Palma, G. ; Ahmadi, A. ; Osborne, Aileen ; Scott, Neil William ; Prescott, Gordon James ; Bennett, Jill ; Semple, Sean ; Dick, Smita ; Mozzoni, P. ; Haites, Neva Elizabeth ; Wettinger, S. Bezzina ; Mutti, A. ; Otelea, M. ; Seaton, Anthony ; Soderkvist, P. ; Felice, A. ; Geoparkinson Study Group. / Gene-environment interactions in parkinsonism and Parkinson's disease : The Geoparkinson study. In: Occupational and Environmental Medicine. 2007 ; Vol. 64, No. 10. pp. 673-680.
@article{85e5f6e67e304481a36169c42bac12c1,
title = "Gene-environment interactions in parkinsonism and Parkinson's disease: The Geoparkinson study",
abstract = "OBJECTIVES: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. RESULTS: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95{\%} CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). CONCLUSIONS: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.",
keywords = "case-control studies, environmental exposure, Europe, female, genetic predisposition to disease, genotype, humans, male, odds ratio, Parkinson Disease, polymorphism, genetic, risk factors, sex distribution",
author = "Dick, {Finlay David} and {De Palma}, G. and A. Ahmadi and Aileen Osborne and Scott, {Neil William} and Prescott, {Gordon James} and Jill Bennett and Sean Semple and Smita Dick and P. Mozzoni and Haites, {Neva Elizabeth} and Wettinger, {S. Bezzina} and A. Mutti and M. Otelea and Anthony Seaton and P. Soderkvist and A. Felice and {Geoparkinson Study Group}",
year = "2007",
month = "10",
doi = "10.1136/oem.2006.032078",
language = "English",
volume = "64",
pages = "673--680",
journal = "Occupational and Environmental Medicine",
issn = "1351-0711",
publisher = "BMJ Publishing Group",
number = "10",

}

TY - JOUR

T1 - Gene-environment interactions in parkinsonism and Parkinson's disease

T2 - The Geoparkinson study

AU - Dick, Finlay David

AU - De Palma, G.

AU - Ahmadi, A.

AU - Osborne, Aileen

AU - Scott, Neil William

AU - Prescott, Gordon James

AU - Bennett, Jill

AU - Semple, Sean

AU - Dick, Smita

AU - Mozzoni, P.

AU - Haites, Neva Elizabeth

AU - Wettinger, S. Bezzina

AU - Mutti, A.

AU - Otelea, M.

AU - Seaton, Anthony

AU - Soderkvist, P.

AU - Felice, A.

AU - Geoparkinson Study Group

PY - 2007/10

Y1 - 2007/10

N2 - OBJECTIVES: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. RESULTS: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). CONCLUSIONS: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.

AB - OBJECTIVES: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. RESULTS: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). CONCLUSIONS: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.

KW - case-control studies

KW - environmental exposure

KW - Europe

KW - female

KW - genetic predisposition to disease

KW - genotype

KW - humans

KW - male

KW - odds ratio

KW - Parkinson Disease

KW - polymorphism, genetic

KW - risk factors

KW - sex distribution

U2 - 10.1136/oem.2006.032078

DO - 10.1136/oem.2006.032078

M3 - Article

VL - 64

SP - 673

EP - 680

JO - Occupational and Environmental Medicine

JF - Occupational and Environmental Medicine

SN - 1351-0711

IS - 10

ER -