title: Association between dopamine D3 receptor gene polymorphisms and schizophrenia in an isolate population.
abstract: There are several lines of evidence implicating the dopamine D3 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<1x 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.
authors.affiliation: Clinical Neuropharmacology PO51, Division of Psych. Medicine, Institute of Psychiatry, KCL, Denmark Hill, London SE5 8AF, UK. s.staddon@iop.kcl.ac.uk
authors.forename: Susan
authors.initials: S
authors.lastname: Staddon
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Arranz
authors.forename: Dalu
authors.initials: D
authors.lastname: Mancama
authors.forename: Fernando
authors.initials: F
authors.lastname: Perez-Nievas
authors.forename: Iñaki
authors.initials: I
authors.lastname: Arrizabalaga
authors.forename: Richard
authors.initials: R
authors.lastname: Anney
authors.forename: Paul
authors.initials: P
authors.lastname: Buckland
authors.forename: Amanda
authors.initials: A
authors.lastname: Elkin
authors.forename: Sarah
authors.initials: S
authors.lastname: Osborne
authors.forename: Janet
authors.initials: J
authors.lastname: Munro
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mata
authors.forename: Robert W
authors.initials: RW
authors.lastname: Kerwin
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011159:Population Surveillance / Q000379:methods; D011618:Psychotic Disorders / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology*; D013030:Spain
chemical_list: C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3