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Environ Res. 2015 Nov;143(Pt A):98-106. doi: 10.1016/j.envres.2015.08.022. Epub 2015 Oct 19.

Genetic variability in ABCB1, occupational pesticide exposure, and Parkinson's disease.

Author information

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

Abstract

BACKGROUND:

Studies suggested that variants in the ABCB1 gene encoding P-glycoprotein, a xenobiotic transporter, may increase susceptibility to pesticide exposures linked to Parkinson's Disease (PD) risk.

OBJECTIVES:

To investigate the joint impact of two ABCB1 polymorphisms and pesticide exposures on PD risk.

METHODS:

In a population-based case control study, we genotyped ABCB1 gene variants at rs1045642 (c.3435C/T) and rs2032582 (c.2677G/T/A) and assessed occupational exposures to organochlorine (OC) and organophosphorus (OP) pesticides based on self-reported occupational use and record-based ambient workplace exposures for 282 PD cases and 514 controls of European ancestry. We identified active ingredients in self-reported occupational use pesticides from a California database and estimated ambient workplace exposures between 1974 and 1999 employing a geographic information system together with records for state pesticide and land use. With unconditional logistic regression, we estimated marginal and joint contributions for occupational pesticide exposures and ABCB1 variants in PD.

RESULTS:

For occupationally exposed carriers of homozygous ABCB1 variant genotypes, we estimated odds ratios of 1.89 [95% confidence interval (CI): (0.87, 4.07)] to 3.71 [95% CI: (1.96, 7.02)], with the highest odds ratios estimated for occupationally exposed carriers of homozygous ABCB1 variant genotypes at both SNPs; but we found no multiplicative scale interactions.

CONCLUSIONS:

This study lends support to a previous report that commonly used pesticides, specifically OCs and OPs, and variant ABCB1 genotypes at two polymorphic sites jointly increase risk of PD.

KEYWORDS:

Epidemiology; Multidrug resistance protein 1 gene (ABCB1); P-glycoprotein; Parkinson’s disease; Pesticide

PMID:
26457621
PMCID:
PMC4911423
DOI:
10.1016/j.envres.2015.08.022
[Indexed for MEDLINE]
Free PMC Article

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