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Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age - The GenePD study

Lookup NU author(s): Professor David BurnORCiD, Professor Patrick Chinnery

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Abstract

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.

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Author(s): Wilk JB, Tobin JE, Suchowersky O, Shill HA, Klein C, Wooten GF, Lew MF, Mark MH, Guttman M, Watts RL, Singer C, Growdon JH, Latourelle JC, Saint-Hilaire MH, DeStefano AL, Prakash R, Williamson S, Berg CJ, Sun M, Goldwurm S, Pezzoli G, Racette BA, Perlmutter JS, Parsian A, Baker KB, Giroux ML, Litvan I, Pramstaller PP, Nicholson G, Burn DJ, Chinnery PF, Vieregge P, Slevin JT, Cambi F, MacDonald ME, Gusella JF, Myers RH, Golbe LI

Publication type: Article

Publication status: Published

Journal: Neurology

Year: 2006

Volume: 67

Issue: 12

Pages: 2206-2210

ISSN (print): 0028-3878

ISSN (electronic): 1526-632X

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1212/01.wnl.0000249149.22407.d1

DOI: 10.1212/01.wnl.0000249149.22407.d1

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