title: Genetic variability in ABCB1, occupational pesticide exposure, and Parkinson's disease.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Narayan
authors.affiliation: 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.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA, USA.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Paul
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA, USA.
authors.forename: Zeyan
authors.initials: Z
authors.lastname: Liew
authors.affiliation: Department of Preventative Medicine, University of Southern California (USC) Keck School of Medicine and Department of Geography, USC, Los Angeles, CA, USA.
authors.forename: Myles
authors.initials: M
authors.lastname: Cockburn
authors.affiliation: Department of Neurology, School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Bronstein
authors.affiliation: 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.
authors.forename: Beate
authors.initials: B
authors.lastname: Ritz
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D003627:Data Interpretation, Statistical; D005260:Female; D014644:Genetic Variation; D040362:Geographic Information Systems; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D010300:Parkinson Disease / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D010575:Pesticides / Q000032:analysis / Q000633:toxicity*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010575:Pesticides
keywords: Epidemiology; Multidrug resistance protein 1 gene (ABCB1); P-glycoprotein; Parkinson’s disease; Pesticide