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Organophosphate pesticides and PON1 L55M in Parkinson's disease progression.

ABSTRACT: BACKGROUND:Parkinson's disease (PD) has motor and non-motor features that contribute to its phenotype and functional decline. Organophosphate (OP) pesticides and PON1 L55M, which influences OP metabolism, have been implicated in multiple mechanisms related to neuronal cell death and may influence PD symptom progression. OBJECTIVE:To investigate whether ambient agricultural OP exposure and PON1 L55M influence the rate of motor, cognitive, and mood-related symptom progression in PD. METHODS:We followed a longitudinal cohort of 246 incident PD patients on average over 5years (7.5years after diagnosis), repeatedly measuring symptom progression with the Mini-Mental State Exam (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), and Geriatric Depressive Scale (GDS). OP exposures were generated with a geographic information system (GIS) based exposure assessment tool. We employed repeated-measures regression to assess associations between OP exposure and/or PON1 L55M genotype and progression. RESULTS:High OP exposures were associated with faster progression of motor (UPDRS ?=0.24, 95% CI=-0.01, 0.49) and cognitive scores (MMSE ?=-0.06, 95% CI=-0.11, -0.01). PON1 55MM was associated with faster progression of motor (UPDRS ?=0.28, 95% CI=0.08, 0.48) and depressive symptoms (GDS ?=0.07; 95% CI=0.01, 0.13). We also found the PON1 L55M variant to interact with OP exposures in influencing MMSE cognitive scores (?=-1.26, 95% CI=-2.43, -0.09). CONCLUSION:Our study provides preliminary support for the involvement of OP pesticides and PON1 in PD-related motor, cognitive, or depressive symptom progression. Future studies are needed to replicate findings and examine whether elderly populations generally are similarly impacted by pesticides or PON1 55M genotypes.

SUBMITTER: Paul KC

PROVIDER: S-EPMC5600289 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Organophosphate pesticides and PON1 L55M in Parkinson's disease progression.

Paul Kimberly C KC Sinsheimer Janet S JS Cockburn Myles M Bronstein Jeff M JM Bordelon Yvette Y Ritz Beate B

Environment international 20170706

<h4>Background</h4>Parkinson's disease (PD) has motor and non-motor features that contribute to its phenotype and functional decline. Organophosphate (OP) pesticides and PON1 L55M, which influences OP metabolism, have been implicated in multiple mechanisms related to neuronal cell death and may influence PD symptom progression.<h4>Objective</h4>To investigate whether ambient agricultural OP exposure and PON1 L55M influence the rate of motor, cognitive, and mood-related symptom progression in PD. ...[more]

PMID: 28689109

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Project description:BackgroundGrowing evidence suggests that exposure to environmental chemicals, such as pesticides, impacts renal function and chronic kidney disease (CKD). However, it is not clear if pesticides may affect CKD progression and no studies exist in children.ObjectivesThe objective of this study was to examine associations between serially measured urinary OP pesticide metabolites and clinical and laboratory measures of kidney function over time among children with CKD.MethodsThis study used data on 618 participants enrolled in the CKD in Children study (CKiD), a cohort study of pediatric CKD patients from the US and Canada. Children were followed over an average of 3.0 years (standard deviation (SD) = 1.6) between 2005 and 2015. In serially collected urine samples over time, six nonspecific dialkyl phosphate (DAP) metabolites of OP pesticides were measured. Biomarkers of tubular injury (kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) and oxidant stress (8-hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostane) were determined in the same specimens. Estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure were assessed annually.ResultsDAPs were associated with increased KIM-1 and 8-OHdG throughout follow-up. A standard deviation increase in ∑diethyl metabolites was associated with increases of 11.9% (95% Confidence Interval (CI): 4.8%, 19.4%) and 13.2% (95% CI: 9.3%, 17.2%) in KIM-1 and 8-OHdG over time, respectively. DAPs were associated with lower eGFR at baseline and higher eGFR over subsequent years.ConclusionsThese findings provide preliminary evidence suggesting that urinary DAP metabolites are associated with subclinical kidney injury among children with CKD, which may signal the potential for clinical events to manifest in the future. The results from this study are significant from both a clinical and public health perspective, given that OP pesticide exposure is a modifiable risk factor.

Dataset Information

Organophosphate pesticides and PON1 L55M in Parkinson's disease progression.

Publications

Organophosphate pesticides and PON1 L55M in Parkinson's disease progression.

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