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

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

Author information

  • 1Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford, CA 94305-5405, USA. vmcguire@stanford.edu

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.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID:
21663922
[PubMed - indexed for MEDLINE]
PMCID:
PMC3155471
Free PMC Article

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