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Organophosphate Pesticide Exposures, Nitric Oxide Synthase Gene Variants, and Gene–Pesticide Interactions in a Case–Control Study of Parkinson’s Disease, California (USA)
- Source :
- Environmental Health Perspectives
- Publication Year :
- 2016
- Publisher :
- Environmental Health Perspectives, 2016.
-
Abstract
- Background: Nitric oxide synthase (NOS) genes are candidates for Parkinson’s disease (PD) because NOS enzymes produce nitric oxide (NO), a pro-oxidant that can damage neurons. Widely used organophosphate (OP) pesticides can induce oxidative stress and are reported to increase PD risk. Additionally, two single nucleotide polymorphisms (SNPs) from the PON1 (paraoxonase 1) gene influence the ability to metabolize OPs. Objective: Here, we investigated contributions of NOS genes and OP pesticides to PD risk, controlling for PON1 status. Methods: In 357 incident PD cases and 495 population controls, we investigated eight NOS SNPs and interactions with both household and ambient agricultural OP exposures assessed with geographic information system (GIS). Results: In comparing PD in homozygous variant carriers of NOS2A rs1060826 versus homozygous wild-type or heterozygotes, we estimate an adjusted odds ratio (OR) of 1.51 (95% CI: 0.95, 2.41). When considering interactions between NOS1 rs2682826 and OP exposure from household use, the OR for frequent OP use alone was 1.30 (95% CI: 0.72, 2.34) and for the CT+TT genotype alone was 0.89 (95% CI: 0.58, 1.39), and for frequent OP use combined with the CT+TT genotype the OR was 2.84 (95% CI: 1.49, 5.40) (interaction p-value 0.04). Similar results were seen for ambient OP exposure. Interactions between OP exposure and three other NOS1 SNPs and a genetic risk score combining all NOS1 SNPs reached statistical significance. Conclusions: We found that OP pesticides were more strongly associated with PD among participants with variant genotypes in NOS1, consistent with the importance of oxidative stress-inducing mechanisms. Our data provide evidence for NOS1 modifying PD risk in OP exposed populations. Citation: Paul KC, Sinsheimer JS, Rhodes SL, Cockburn M, Bronstein J, Ritz B. 2016. Organophosphate pesticide exposures, nitric oxide synthase gene variants, and gene–pesticide interactions in a case–control study of Parkinson’s disease, California (USA). Environ Health Perspect 124:570–577; http://dx.doi.org/10.1289/ehp.1408976
- Subjects :
- 0301 basic medicine
Parkinson's disease
Health, Toxicology and Mutagenesis
Nitric Oxide Synthase Type II
010501 environmental sciences
Pharmacology
Polymorphism, Single Nucleotide
01 natural sciences
California
Nitric oxide
03 medical and health sciences
chemistry.chemical_compound
Organophosphorus Compounds
Risk Factors
medicine
Humans
Pesticides
Gene
0105 earth and related environmental sciences
2. Zero hunger
chemistry.chemical_classification
biology
Aryldialkylphosphatase
Research
Organophosphate
Public Health, Environmental and Occupational Health
Parkinson Disease
Environmental Exposure
Environmental exposure
Pesticide
medicine.disease
3. Good health
Nitric oxide synthase
030104 developmental biology
Enzyme
chemistry
Biochemistry
Case-Control Studies
biology.protein
Environmental Pollutants
Nitric Oxide Synthase
Subjects
Details
- ISSN :
- 15529924 and 00916765
- Volume :
- 124
- Database :
- OpenAIRE
- Journal :
- Environmental Health Perspectives
- Accession number :
- edsair.doi.dedup.....050220339e314a9c3e7c0a4a9a0c4517