Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium

J Neurol Sci. 2011 Aug 15;307(1-2):22-9. doi: 10.1016/j.jns.2011.05.031. Epub 2011 Jun 12.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • African Americans / genetics
  • Aged
  • Case-Control Studies
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Hispanic Americans / genetics
  • Humans
  • Male
  • Middle Aged
  • Multigene Family / genetics
  • North America / epidemiology
  • Parkinson Disease / epidemiology
  • Parkinson Disease / ethnology*
  • Parkinson Disease / genetics*
  • Polymorphism, Genetic / genetics*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D3 / genetics*
  • Risk Assessment / methods

Substances

  • Receptors, Dopamine D2
  • Receptors, Dopamine D3