title: Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium.
abstract: OBJECTIVE
  To examine genetic associations of polymorphisms in the dopamine receptor D2 (DRD2) and D3 (DRD3) genes with risk of Parkinson's disease (PD).
  
  
  METHODS
  The study included 1325 newly diagnosed patients with PD and 1735 controls from a consortium of five North American case-control studies. We collected risk factor information by in-person or telephone interview. Six DRD2 and two DRD3 polymorphisms were genotyped using a common laboratory. Odds ratios were estimated using logistic regression.
  
  
  RESULTS
  Among non-Hispanic whites, homozygous carriers of Taq1A DRD2 (rs1800497) polymorphism had an increased risk of PD compared to homozygous wildtype carriers (OR=1.5, 95% CI 1.0-2.3). In contrast, the direction of association for Taq1A polymorphism was opposite for African-Americans, showing an inverse association with PD risk (OR=0.10, 95% CI 0.2-0.7). Among white Hispanics who carried two alleles, the Ser9Gly DRD3 (rs6280) polymorphism was associated with a decreased risk of PD (OR=0.4, 95% CI 0.2-0.8). The inverse association of smoking with PD risk was not modified by any of the DRD2 or DRD3 polymorphisms.
  
  
  CONCLUSIONS
  DRD2 polymorphisms are unlikely to be true disease-causing variants; however, three DRD2 polymorphisms (including Taq1A) may be in linkage disequilibrium with possible disease associated variants in the DRD2-ANKK1-NCAM1-TTC12 gene cluster.
authors.affiliation: Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford, CA 94305-5405, USA. vmcguire@stanford.edu
authors.forename: V
authors.initials: V
authors.lastname: McGuire
authors.forename: S K
authors.initials: SK
authors.lastname: Van Den Eeden
authors.forename: C M
authors.initials: CM
authors.lastname: Tanner
authors.forename: F
authors.initials: F
authors.lastname: Kamel
authors.forename: D M
authors.initials: DM
authors.lastname: Umbach
authors.forename: K
authors.initials: K
authors.lastname: Marder
authors.forename: R
authors.initials: R
authors.lastname: Mayeux
authors.forename: B
authors.initials: B
authors.lastname: Ritz
authors.forename: G W
authors.initials: GW
authors.lastname: Ross
authors.forename: H
authors.initials: H
authors.lastname: Petrovitch
authors.forename: B
authors.initials: B
authors.lastname: Topol
authors.forename: R A
authors.initials: RA
authors.lastname: Popat
authors.forename: S
authors.initials: S
authors.lastname: Costello
authors.forename: A D
authors.initials: AD
authors.lastname: Manthripragada
authors.forename: A
authors.initials: A
authors.lastname: Southwick
authors.forename: R M
authors.initials: RM
authors.lastname: Myers
authors.forename: L M
authors.initials: LM
authors.lastname: Nelson
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics; D009656:North America / Q000453:epidemiology; D010300:Parkinson Disease / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods; D044465:White People / Q000235:genetics
chemical_list: D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3