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Research Article

Genetic modification of the association of paraquat and Parkinson's disease †‡

  1. Samuel M. Goldman MD, MPH1,*,
  2. Freya Kamel PhD, MPH2,
  3. G. Webster Ross MD3,
  4. Grace S. Bhudhikanok PhD1,
  5. Jane A. Hoppin ScD2,
  6. Monica Korell MPH1,
  7. Connie Marras MD, PhD4,
  8. Cheryl Meng MS1,
  9. David M. Umbach PhD5,
  10. Meike Kasten MD6,
  11. Anabel R. Chade MD7,
  12. Kathleen Comyns MPH1,
  13. Marie B. Richards PhD8,
  14. Dale P. Sandler PhD2,
  15. Aaron Blair PhD9,
  16. J. William Langston MD1,
  17. Caroline M. Tanner MD, PhD1

Article first published online: 8 OCT 2012

DOI: 10.1002/mds.25216

Issue

Movement Disorders

Movement Disorders

Volume 27, Issue 13, pages 1652–1658, November 2012

Additional Information

How to Cite

Goldman, S. M., Kamel, F., Ross, G. W., Bhudhikanok, G. S., Hoppin, J. A., Korell, M., Marras, C., Meng, C., Umbach, D. M., Kasten, M., Chade, A. R., Comyns, K., Richards, M. B., Sandler, D. P., Blair, A., Langston, J. W. and Tanner, C. M. (2012), Genetic modification of the association of paraquat and Parkinson's disease . Mov. Disord., 27: 1652–1658. doi: 10.1002/mds.25216

Author Information

  1. 1

    The Parkinson's Institute, Sunnyvale, California, USA

  2. 2

    Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA

  3. 3

    Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA

  4. 4

    Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada

  5. 5

    Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina, USA

  6. 6

    Departments of Neurology and Clinical and Molecular Neurogenetics, University of Lübeck, Lübeck, Germany

  7. 7

    Institute of Cognitive Neurology, Institute of Neuroscience, Favaloro University, Buenos Aires, Argentina

  8. 8

    Westat Inc., Durham, North Carolina, USA

  9. 9

    Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA

*The Parkinson's Institute, 675 Almanor Avenue, Sunnyvale, CA 94085, USA

  1. †

    Relevant conflicts of interest/financial disclosures: Nothing to report.

  2. ‡

    Full financial disclosures and author roles may be found in the online version of this article.

Publication History

  1. Issue published online: 27 NOV 2012
  2. Article first published online: 8 OCT 2012
  3. Manuscript Accepted: 30 AUG 2012
  4. Manuscript Revised: 22 AUG 2012
  5. Manuscript Received: 31 MAY 2012

Funded by

  • Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS). Grant Numbers: Z01-ES044007, Z01-ES049030
  • a National Cancer Institute grant. Grant Number: Z01-CP010119
  • NIEHS grants. Grant Numbers: R01-ES10803, U54 ES012077
  • the Michael J. Fox Foundation

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Keywords:

  • Parkinson's disease;
  • paraquat;
  • glutathione transferase;
  • pesticide;
  • gene-environment interaction

Abstract

Paraquat is one of the most widely used herbicides worldwide. It produces a Parkinson's disease (PD) model in rodents through redox cycling and oxidative stress (OS) and is associated with PD risk in humans. Glutathione transferases provide cellular protection against OS and could potentially modulate paraquat toxicity. We investigated PD risk associated with paraquat use in individuals with homozygous deletions of the genes encoding glutathione S-transferase M1 (GSTM1) or T1 (GSTT1). Eighty-seven PD subjects and 343 matched controls were recruited from the Agricultural Health Study, a study of licensed pesticide applicators and spouses in Iowa and North Carolina. PD was confirmed by in-person examination. Paraquat use and covariates were determined by interview. We genotyped subjects for homozygous deletions of GSTM1 (GSTM1*0) and GSTT1 (GSTT1*0) and tested interaction between paraquat use and genotype using logistic regression. Two hundred and twenty-three (52%) subjects had GSTM1*0, 95 (22%) had GSTT1*0, and 73 (17%; all men) used paraquat. After adjustment for potential confounders, there was no interaction with GSTM1. In contrast, GSTT1 genotype significantly modified the association between paraquat and PD. In men with functional GSTT1, the odds ratio (OR) for association of PD with paraquat use was 1.5 (95% confidence interval [CI]: 0.6–3.6); in men with GSTT1*0, the OR was 11.1 (95% CI: 3.0–44.6; P interaction: 0.027). Although replication is needed, our results suggest that PD risk from paraquat exposure might be particularly high in individuals lacking GSTT1. GSTT1*0 is common and could potentially identify a large subpopulation at high risk of PD from oxidative stressors such as paraquat. © 2012 Movement Disorder Society

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