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Association between dopamine D3 receptor gene polymorphisms and schizophrenia in an isolate population

Staddon, Susan, Arranz, Maria J., Mancama, Dalu, Perez-Nievas, Fernando, Arrizabalaga, Iñaki, Anney, Richard, Buckland, Paul Robert, Elkin, Amanda, Osborne, Sarah, Munro, Janet, Mata, Ignacio and Kerwin, Robert W. 2005. Association between dopamine D3 receptor gene polymorphisms and schizophrenia in an isolate population. Schizophrenia Research 73 (1) , pp. 49-54. 10.1016/j.schres.2004.06.011

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Abstract

There are several lines of evidence implicating theD3 receptor in the pathophysiology of schizophrenia. The Ser9Gly polymorphism of the dopamine D3 receptor gene (DRD3) has been the most extensively investigated DRD3 variant in connection with the disease but results have been inconclusive. Recent reports indicate that the Ser9Gly polymorphism is in linkage disequilibrium with other markers, but association studies between DRD3 haplotypes and schizophrenia have had mixed results. Genetic heterogeneity may be one of the causes of contradicting results. In order to clarify the role of DRD3 alterations in the aetiology of disease, we have investigated three D3 genetic variants (Ser9Gly, −205-G/A, −7685-G/C) in a sample of patients with schizophrenia or schizoaffective disorder (N=118) and controls (N=162) recruited from a human isolate from Navarra (Northern Spain) of Basque origin. Although no association was found between the Ser9Gly or the −205-A/G polymorphisms and disease, an excess of allele −7685-C was observed in patients (p=0.002 after correction for multiple analyses). Haplotype analysis shows the three markers to be in strong linkage disequilibrium (p<0.0001) and strongly associated with disease (p<1×10−5). These results may suggest that these polymorphisms exert a combined or synergistic effect on susceptibility to schizophrenia, or are in linkage with an unknown causative factor. However, further replication in independent samples is required.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Polymorphism; DRD3; Haplotypes; Schizophrenia; Genetic association; Basque; Human isolate
Publisher: Elsevier
ISSN: 0920-9964
Last Modified: 05 Feb 2020 03:36
URI: http://orca.cf.ac.uk/id/eprint/57461

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