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Occup Environ Med 2007;64:673-680 doi:10.1136/oem.2006.032078
  • Original article

Gene-environment interactions in parkinsonism and Parkinson’s disease: the Geoparkinson study

  1. F D Dick1,
  2. G De Palma4,
  3. A Ahmadi6,
  4. A Osborne2,
  5. N W Scott3,
  6. G J Prescott3,
  7. J Bennett3,
  8. S Semple1,
  9. S Dick1,
  10. P Mozzoni5,
  11. N Haites2,
  12. S Bezzina Wettinger8,
  13. A Mutti4,
  14. M Otelea7,
  15. A Seaton1,
  16. P Soderkvist6,
  17. A Felice8
  1. 1
    Department of Environmental and Occupational Medicine, University of Aberdeen, UK
  2. 2
    Department of Medical Genetics, University of Aberdeen, UK
  3. 3
    Department of Public Health, University of Aberdeen, UK
  4. 4
    Department of Clinical Medicine, Nephrology and Health Science, Laboratory of Industrial Toxicology, University of Parma, Parma, Italy
  5. 5
    ISPESL Research Centre, University of Parma, Parma, Italy
  6. 6
    Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Linköping, Sweden
  7. 7
    Department of Occupational Medicine, University Hospital ‘Colentina, Bucharest, Romania
  8. 8
    Laboratory of Molecular Genetics, Department of Physiology and Biochemistry, University of Malta, Msida, Malta
  1. Finlay D Dick, Department of Environmental and Occupational Medicine, University of Aberdeen, Foresterhill, Aberdeen, UK; f.dick{at}abdn.ac.uk
  • Accepted 4 April 2007
  • Final version accepted 20 April 2007
  • Published Online First 20 April 2007

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.

Footnotes

  • This study was funded by the European Union as part of the Fifth Framework programme, project number QLK4-CT-1999-01133. We gratefully acknowledge the support of the European Union for this project.

  • Competing interest: None.

  • Abbreviations:
    AAI
    average annual intensity
    bp
    base pair
    CE
    cumulative exposure
    HWE
    Hardy-Weinberg equilibrium
    JEM
    job exposure matrix
    OEL
    occupational exposure limit
    OR
    odds ratios
    PCR
    polymerase chain reaction
    PD
    Parkinson’s disease
    RFLP
    restriction fragment length polymorphism

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