title: Dopamine transporter genetic variants and pesticides in Parkinson's disease.
abstract: BACKGROUND
  Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson's disease (PD) risk.
  
  
  METHODS
  
  
  
  METHODS
  In 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.
  
  
  RESULTS
  PD 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.
  
  
  CONCLUSIONS
  Using 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.
  
  
  CONCLUSIONS
  Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.
authors: Department of Epidemiology, Center for Occupational and Environmental Health, UCLA School of Public Health, University of California at Los Angeles, Los Angeles, California 90095-1772, USA. britz@ucla.edu
authors: Beate R
authors: BR
authors: Ritz
authors: Angelika D
authors: AD
authors: Manthripragada
authors: Sadie
authors: S
authors: Costello
authors: Sarah J
authors: SJ
authors: Lincoln
authors: Matthew J
authors: MJ
authors: Farrer
authors: Myles
authors: M
authors: Cockburn
authors: Jeff
authors: J
authors: Bronstein
mesh_terms: D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008344:Maneb / Q000633:toxicity; D008875:Middle Aged; D010269:Paraquat / Q000633:toxicity; D010300:Parkinson Disease / Q000235:genetics*; D010575:Pesticides / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D004785:Environmental Pollutants; D010575:Pesticides; D008344:Maneb; D010269:Paraquat