Organophosphate Pesticide Exposures, Nitric Oxide Synthase Gene Variants, and Gene-Pesticide Interactions in a Case-Control Study of Parkinson's Disease, California (USA)
| Autor: | Paul, KC, Sinsheimer, JS, Rhodes, SL, Cockburn, M, Bronstein, J, Ritz, B |
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| Rok vydání: | 2016 |
| Předmět: |
Aging
Nitric Oxide Synthase Type II Rural Health Neurodegenerative Toxicology Medical and Health Sciences California Organophosphorus Compounds Risk Factors Genetics Humans 2.1 Biological and endogenous factors Climate-Related Exposures and Conditions Aetiology Pesticides Polymorphism Parkinson's Disease Aryldialkylphosphatase Prevention Neurosciences Parkinson Disease Environmental Exposure Single Nucleotide Brain Disorders Case-Control Studies Environmental Pollutants Nitric Oxide Synthase Environmental Sciences |
| Zdroj: | Environmental health perspectives, vol 124, iss 5 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). ENVIRONMENTAL HEALTH PERSPECTIVES, 124(5), 570-577. doi: 10.1289/ehp.1408976. UCLA: Retrieved from: http://www.escholarship.org/uc/item/56j1z2m6 |
| Popis: | BackgroundNitric 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.ObjectiveHere, we investigated contributions of NOS genes and OP pesticides to PD risk, controlling for PON1 status.MethodsIn 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).ResultsIn 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.ConclusionsWe 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.CitationPaul 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. |
| Databáze: | OpenAIRE |
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