Format

Send to

Choose Destination
Environ Int. 2017 Oct;107:75-81. doi: 10.1016/j.envint.2017.06.018. Epub 2017 Jul 6.

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

Author information

1
Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, USA.
2
Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, California, USA; Departments of Human Genetics and Biomathematics, David Geffen School of Medicine, Los Angeles, California, USA.
3
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, CA, USA.
4
Department of Neurology, David Geffen School of Medicine, Los Angeles, California, USA.
5
Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, USA; Department of Neurology, David Geffen School of Medicine, Los Angeles, California, USA. Electronic address: britz@ucla.edu.

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 β=0.24, 95% CI=-0.01, 0.49) and cognitive scores (MMSE β=-0.06, 95% CI=-0.11, -0.01). PON1 55MM was associated with faster progression of motor (UPDRS β=0.28, 95% CI=0.08, 0.48) and depressive symptoms (GDS β=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 (β=-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.

KEYWORDS:

Cognitive decline; Organophosphates; PON1; Parkinson's disease; Progression

PMID:
28689109
PMCID:
PMC5600289
[Available on 2018-10-01]
DOI:
10.1016/j.envint.2017.06.018
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center