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NEUROLOGY 2006;67:2206-2210
© 2006 American Academy of Neurology

Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age

The GenePD Study

J. B. Wilk, DSc, J. E. Tobin, BA, O. Suchowersky, MD, H. A. Shill, MD, C. Klein, MD, G. F. Wooten, MD, M. F. Lew, MD, M. H. Mark, MD, M. Guttman, MD, R. L. Watts, MD, C. Singer, MD, J. H. Growdon, MD, J. C. Latourelle, MS, M. H. Saint-Hilaire, MD, A. L. DeStefano, PhD, R. Prakash, MS, S. Williamson, BS, C. J. Berg, BS, M. Sun, MD, PhD, S. Goldwurm, MD, PhD, G. Pezzoli, MD, B. A. Racette, MD, J. S. Perlmutter, MD, A. Parsian, PhD, K. B. Baker, PhD, M. L. Giroux, MD, I. Litvan, MD, P. P. Pramstaller, MD, G. Nicholson, PhD, D. J. Burn, MD, P. F. Chinnery, MD, P. Vieregge, PhD, J. T. Slevin, MD, F. Cambi, MD, PhD, M. E. MacDonald, PhD, J. F. Gusella, PhD, R. H. Myers, PhD and L. I. Golbe, MD

From the Department of Neurology (J.B.W., J.E.T., J.C.L., M.H.S.-H., A.L.D., R.P., S.W., C.J.B., R.H.M.), Department of Anatomy and Neurobiology (J.E.T.), Boston University School of Medicine, Department of Biostatistics (A.L.D.), Boston University School of Public Health Boston, MA; Departments of Clinical Neurosciences and Medical Genetics (O.S.), University of Calgary, Calgary, Alberta, Canada; Muhammad Ali Parkinson Center (H.A.S.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (C.K.), University of Lübeck, Lübeck, Germany; Department of Neurology (G.F.W.), University of Virginia Health System, Charlottesville, VA; Department of Neurology (M.F.L.), University of Southern California, Los Angeles, CA; Department of Neurology (L.I.G., M.H.M.), University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ; Department of Medicine (M.G.), University of Toronto, Toronto, Canada; Department of Neurology (R.L.W.), University of Alabama at Birmingham, Birmingham, AL; Department of Neurology (C.S.), University of Miami, Miami, FL; Department of Neurology (J.H.G.) and Molecular Neurogenetics Unit, Center for Human Genetic Research (M.S., M.E.M., J.F.G.), Massachusetts General Hospital, Harvard Medical School Boston, MA; Parkinson Institute (S.G., G.P.), Istituti Clinici di Perfezionamento, Milano, Italy; Department of Neurology (B.A.R., J.S.P.), Washington University School of Medicine, Saint Louis, MO; Department of Pediatrics (A.P.), Human Genomics Laboratories, University of Arkansas for Medical Sciences, AR; Departments of Neurology and Neuroscience (K.B.B., M.L.G.), Cleveland Clinic Foundation, Cleveland, OH; Department of Neurology (I.L.), University of Louisville School of Medicine, Louisville, KY; Department of Neurology (P.P.P.), General Regional Hospital Bolzano, Bolzano, Italy; Neurology Department (G.N.), University of Sydney ANZAC Research Institute, Concord Hospital, Sydney, Australia; Regional Neurosciences Centre (D.J.B., P.F.C.), Newcastle General Hospital, Newcastle upon Tyne, UK; Klinik fur Neurologie (P.V.), Klinikum Lippe-Lemgo, Lemgo, Germany; Department of Neurology (F.C., J.T.S.), University of Kentucky College of Medicine, and Veterans Affairs Medical Center (J.T.S.), Lexington, KY.

Address correspondence and reprint requests to Dr. Jemma B. Wilk, Department of Neurology, Boston University School of Medicine, 715 Albany St., E-338, Boston, MA 02118; e-mail: jwilk{at}bu.edu.

Background: Polymorphisms in the glutathione S-transferase pi gene (GSTP1), encoding GSTP1-1, a detoxification enzyme, may increase the risk of Parkinson disease (PD) with exposure to pesticides. Using the GenePD Study sample of familial PD cases, we explored whether GSTP1 polymorphisms were associated with the age at onset of PD symptoms and whether that relation was modified by exposure to herbicides.

Methods: Seven single-nucleotide polymorphisms (SNPs) were genotyped and tested for association with PD onset age in men in three strata: no exposure to herbicides, residential exposure to herbicides, and occupational exposure to herbicides. Haplotypes were similarly evaluated in stratified analyses.

Results: Three SNPs were associated with PD onset age in the group of men occupationally exposed to herbicides. Three additional SNPs had significant trends for the association of PD onset age across the herbicide exposure groups. Haplotype results also provided evidence that the relation between GSTP1 and onset age is modified by herbicide exposure. One haplotype was associated with an approximately 8-years-earlier onset in the occupationally exposed group and a 2.8-years-later onset in the nonexposed group.

Conclusions: Herbicide exposure may be an effect modifier of the relation between glutathione S-transferase pi gene polymorphisms and onset age in familial PD.

Supported by the Bumpus Foundation, PHS grant R01 NS36711-05 "Genetic Linkage Study in PD." The DNA samples contributed by the Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy, were from the Human Genetic Bank of Patients Affected by PD and Parkinsonisms, supported by the Italian Telethon Foundation (grant n. GTF04007). A portion of this research was conducted using the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the NIH NCRR (National Center for Research Resources) Shared Instrumentation grant (1S10RR163736-01A1).

Disclosure: The authors report no conflicts of interest.

Received April 24, 2006. Accepted in final form September 12, 2006.




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