Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 34, Issue 1, Pages 26-31Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2009.09.008
Keywords
Dopamine D2 receptor; Dopamine D3 receptor; Dopamine transporter; Genetic association; Schizophrenia
Funding
- Oviedo University [NP-01-519-3, MB-05-519]
- Instituto de Salud Carlos III
- Centro de Investigacion Biomedica en Red de Salud Mental, CIBERSAM
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Objective: To investigate the association between dopaminergic polymorphisms [DRD2 - 141C Ins/Del, DRD3 Ser9Gly, and SLC6A3 VNTR] and schizophrenia. Methods:Two hundred and eighty-eight outpatients with schizophrenia (DSM-IV criteria) [mean age (SD) = 36.4 (12.4), 60.1% males] and 421 unrelated healthy controls [mean age (SD) = 40.6 (11.3), 51.3% males] from a homogeneous Spanish Caucasian population were genotyped using standard methods. Results: There was a significant difference in genotype distribution for the DRD2 - 141C Ins/Del polymorphism [(chi(2) (2) = 12.35, corrected p = 0.012]. The - 141C Del allele was more common in patients than in controls [0.19 vs. 0.13; chi(2) (1) = 9.14, corrected p = 0.018, OR (95% CI) = 1.57 (1.17-2.10)]. Genotype and allele distributions for DRD3 Ser9Gly and SLC6A3 VNTR polymorphisms were similar in both groups. However, there was tentative evidence of an interaction effect between DRD3 Ser9Gly and SLC6A3 VNTR [Wald = 9.56 (4), p = 0.049]. Compared to the SLC6A3 10/10 genotype category, the risk of schizophrenia was halved among those with 9/10 [OR = 0.51 (95% CI = 0.30-0.89). p = 0.017]. This protective effect was only present in combination with DRD3 Ser/Ser genotype because of the significant interaction between 9/10 and both Ser/Gly [OR= 2.45 (95% CI = 1.16-5.17), p = 0.019] and Gly/Gly [OR = 3.80 (95% CI = 1.24-11.63), p = 0.019]. Conclusions: This study provides evidence that a genetic variant in the DRD2 gene and possible interaction between DRD3 and SLC6A3 genes are associated with schizophrenia. These findings warrant examination in replication studies. (C) 2009 Elsevier Inc. All rights reserved.
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