Journal
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 307, Issue 1-2, Pages 22-29Publisher
ELSEVIER
DOI: 10.1016/j.jns.2011.05.031
Keywords
Parkinson's disease; Dopamine receptor genes; Case-control studies; Epidemiology
Categories
Funding
- Michael J. Fox Foundation for Parkinson's Research
- NIH [NS R01-31964, ES R03-13970, R01-NS32527, ES10544]
- Tobacco-Related Disease Research Fund [8RT-0131, 11RT-0237]
- SCEHSC [5P30 ES07048]
- Parkinson's Disease Association
- United States Department of the Army [DAMD17-98-1-8621, NIA NO1-AG-4-2149, NINDSR01-NS41265, NHLBINO1-HC-05102]
- Office of Research and Development, Medical Research Service, Veterans Affairs
- NIH
- NCI (Division of Cancer Epidemiology and Genetics) [U54-ES12077]
- [NIAPO1 AG07232]
- [U54-ES12078]
- [NIEHS01-ES10803]
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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. (C) 2011 Elsevier B.V. All rights reserved.
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