Well-Water Consumption and Parkinson’s Disease in Rural California

IntroductionInvestigators have hypothesized that consuming pesticide-contaminated well water plays a role in Parkinson's disease (PD), and several previous epidemiologic studies support this hypothesis.ObjectivesWe investigated whether consuming water from private wells located in areas with documented historical pesticide use was associated with an increased risk of PD.MethodsWe employed a geographic information system (GIS)-based model to estimate potential well-water contamination from agricultural pesticides among 368 cases and 341 population controls enrolled in the Parkinson's Environment and Genes Study (PEG). We separately examined 6 pesticides (diazinon, chlorpyrifos, propargite, paraquat, dimethoate, and methomyl) from among 26 chemicals selected for their potential to pollute groundwater or for their interest in PD, and because at least 10% of our population was exposed to them.ResultsCases were more likely to have consumed private well water and to have consumed it on average 4.3 years longer than controls (p = 0.02). High levels of possible well-water contamination with methomyl [odds ratio (OR) = 1.67; 95% confidence interval (CI), 1.00-2.78]), chlorpyrifos (OR = 1.87; 95% CI, 1.05-3.31), and propargite (OR = 1.92; 95% CI, 1.15-3.20) resulted in approximately 70-90% increases in relative risk of PD. Adjusting for ambient pesticide exposures only slightly attenuated these increases. Exposure to a higher number of water-soluble pesticides and organophosphate pesticides also increased the relative risk of PD.ConclusionOur study, the first to use agricultural pesticide application records, adds evidence that consuming well water presumably contaminated with pesticides may play a role in the etiology of PD

Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease

BackgroundResearch suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson's disease (PD) risk.MaterialsMethodsIn 324 incident PD patients and 334 population controls from our rural California case-control study, we genotyped rs2652510, rs2550956 (for the DAT 5' clades), and the 3' variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele-pesticide interactions.ResultsPD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08-2.57] and 3' VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96-3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88-10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70-12.1). We obtained similar results for occupational pesticide measures.DiscussionUsing two independent pesticide measures, we a) replicated previously reported gene-environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.ConclusionOur results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk

Statin use and Parkinson's disease in Denmark

OBJECTIVE: To investigate whether statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) use is associated with risk of Parkinson’s disease (PD) in Denmark. METHODS: We identified 1,931 patients with a first time diagnosis of PD reported in hospital or outpatient clinic records between 2001– 2006. We density matched to these patients 9,651 population controls by birth year and sex relying on the Danish population register. For every participant, we identified pharmacy records of statin and anti-Parkinson drug prescriptions since 1995 and prior to index date from a prescription medication use database for all Danish residents. Whenever applicable, the index dates for cases and their corresponding controls were advanced to the date of first recorded prescription for anti-Parkinson drugs. In our primary analyses, we excluded all statin prescriptions 2-years before PD diagnosis. RESULTS: In unconditional logistic regression analyses adjusting for matching factors and co-morbidities, we observed none to slightly inverse associations between PD diagnosis and statin prescription drug use. Inverse associations with statin use were only observed for short-term (≤1 yrs) statin users (2-year lag OR 0.57; 95% CI 0.36 to 0.89); and suggested at higher intensity statin use (2-year lag OR 0.69; 95% CI 0.45–1.04). No associations were seen among longer-term users and no difference by sex, age, or type of statins used (lipophilic/hydrophilic). CONCLUSION: We found little evidence for a neuroprotective role of statins in PD except for short-term or high intensity users. Yet, further investigations into the contributions of intensity, duration, and lag periods of statin use may still be warranted

α-Synuclein Gene May Interact with Environmental Factors in Increasing Risk of Parkinson’s Disease

BACKGROUND: Although of great interest and suggested in prior reports, possible α-synuclein (SNCA) gene-environment interactions have not been well investigated in humans. METHODS: We used a population-based approach to examine whether the risk of Parkinson's disease (PD) depended on the combined presence of SNCA variations and two important environmental factors, pesticide exposures and smoking. RESULTS/CONCLUSIONS: Similar to recent meta- and pooled analyses, our data suggest a lower PD risk in subjects who were either homozygous or heterozygous for the SNCA REP1 259 genotype, and a higher risk in subjects who were either homozygous or heterozygous for the REP1 263 genotype, especially among subjects with an age of onset ≤68 years. More importantly, while analyses of interactions were limited by small cell sizes, risk due to SNCA variations seemed to vary with pesticide exposure and smoking, especially in younger onset cases, suggesting an age-of-onset effect