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Review
. 2016 Mar;3(1):40-52.
doi: 10.1007/s40572-016-0083-2.

Of Pesticides and Men: a California Story of Genes and Environment in Parkinson's Disease

Beate R Ritz  1   2   3 , Kimberly C Paul  4 , Jeff M Bronstein  5
Affiliations
Review

Of Pesticides and Men: a California Story of Genes and Environment in Parkinson's Disease

Beate R Ritz et al. Curr Environ Health Rep. 2016 Mar.

Abstract

At the start of the postgenomics era, most Parkinson's disease (PD) etiology cannot be explained by our knowledge of genetic or environmental factors alone. For more than a decade, we have explored gene-environment (GxE) interactions possibly responsible for the heterogeneity of genetic as well as environmental results across populations. We developed three pesticide exposure measures (ambient due to agricultural applications, home and garden use, and occupational use) in a large population-based case-control study of incident PD in central California. Specifically, we assessed interactions with genes responsible for pesticide metabolism (PON1); transport across the blood-brain barrier (ABCB1); pesticides interfering with or depending on dopamine transporter activity (DAT/SLC6A3) and dopamine metabolism (ALDH2); impacting mitochondrial function via oxidative/nitrosative stress (NOS1) or proteasome inhibition (SKP1); and contributing to immune dysregulation (HLA-DR). These studies established some specificity for pesticides' neurodegenerative actions, contributed biologic plausibility to epidemiologic findings, and identified genetically susceptible populations.

Keywords: Gene–environment interactions; Parkinson’s disease; Pesticides.

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Conflict of interest statement

Conflict of Interest

BR Ritz, KC Paul, and JM Bronstein declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Proposed Parkinson’s disease pathological mechanisms involving discussed GxE reports
See this image and copyright information in PMC

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References

    1. Caudle WM, Guillot TS, Lazo CR, et al. Industrial toxicants and Parkinson’s disease. Neurotoxicology. 2012;33:178–88. - PMC - PubMed
    1. Lill CM, Roehr JT, McQueen MB, et al. Comprehensive research synopsis and systematic meta-analyses in Parkinson’s disease genetics: The PDGene database. PLoS Genet. 2012;8:e1002548. This study provides an exhaustive summary of the status of PD genetics on more than seven million polymorphisms originating from GWAS or smaller scale PD association studies. - PMC - PubMed
    1. Goldman SM. Environmental toxins and Parkinson’s disease. Annu Rev Pharmacol Toxicol. 2014;54:141–64. - PubMed
    1. Nalls MA, Pankratz N, Lill CM, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet. 2014;46:989–93. - PMC - PubMed
    1. Langston JW, Ballard P, Tetrud JW, et al. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219:979–80. This study was the first to describe a specific toxicant as acting selectively on dopamine neurons. - PubMed

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