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.

Polymorphisms of DRD2 and DRD3 genes and Parkinson’s disease: A meta-analysis

“…Although power analyses showed our meta-analyses have much larger power than that of each of the individual studies, we did not exclude the possibility of false-negative results in the meta-analyses for DRD2 rs6278 (power= 0.637) and rs1799732 (power=0.313). We excluded 9 stages that failed to meet HWE in their control samples (36). We also performed subgroup analyses by ethnicity for DRD2 rs1800497, rs1079597 and DRD3 rs6280.…”

“…There are five subtypes of G-proteincoupled dopamine receptors (DRD1-5) comprising D-1-like (DRD1 and DRD5) and D-2-like (DRD2-4). Among these subtypes, DRD2 (25-36) located on chromosome 11q23 and DRD3 (33,(35)(36)(37)(38)(39)(40) located on chromosome 3q13.3 are the most studied in the association tests of PD.…”

Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson’s disease patients

“…This aspect needs further exploration as the current study was not primarily intended to study such an association. In a large, multiethnic cohort, DRD3 p.Ser9Gly (rs6280) GG variant decreased the risk of developing PD in white Hispanic population [29]. The same study identified opposing effects of another polymorphism Taq1A DRD2 (rs1800497) in two different ethnic groups, increasing the risk of PD in white-non Hispanics but protective in African Americans [29].…”

“…In a large, multiethnic cohort, DRD3 p.Ser9Gly (rs6280) GG variant decreased the risk of developing PD in white Hispanic population [29]. The same study identified opposing effects of another polymorphism Taq1A DRD2 (rs1800497) in two different ethnic groups, increasing the risk of PD in white-non Hispanics but protective in African Americans [29]. Thus the association of DRD3 polymorphisms with PD needs further study in different ethnic groups to arrive at valid conclusions.…”

La Enfermedad de Parkinson: Etiología, Tratamientos y Factores Preventivos

“…Por lo general esta neurodegeneración inicia varios años antes de ser sintomática, siendo entonces muy difícil discriminar con exactitud las causas. En estas circunstancias no es posible establecer las causas por las cuales un determinado paciente desarrolla la patología, ya que a lo largo de su vida pudo haber sido expuesto a muchos agentes tóxicos, o inclusive, a la interacción entre ellos, además de ser posible que presente una predisposición genética que le haya conferido cierta vulnerabilidad neuronal a la neurodegeneración dopaminérgica (Kumar, Djarmati-Westenberger, & Grunewald, 2011;Laing, 2001;McGuire et al, 2011).…”