EUROPEAN MULTICENTER ASSOCIATION STUDY OF SCHIZOPHRENIA - A STUDY OF THE DRD2 SER311CYS AND DRD3 SER9GLY POLYMORPHISMS

As part of the European Multicentre Association Study of Schizophrenia (EMASS), we studied polymorphisms in the dopamine DRD2 and DRD3 recep tor genes, The EMASS collaboration was established to create a large, statistically powerful sample of schizophrenic patients and controls f rom different European centres. Previous studies have suggested associ ations between schizophrenia and the Ser311Cys polymorphism in exon 7 of the dopamine DRD2 receptor gene [Arinami et al., (1994): Lancet 343 :703-704] and a polymorphism Ser9gly in exon 1 of the dopamine DRD3 re ceptor gene [Crocq et al, (1992): J Med Genet 29:858-860], We tested f or these associations in samples of 373 and 413, and 311 and 306 patie nts and controls, respectively, We found no evidence for allelic assoc iation between schizophrenia and the Cys311 variant of the DRD2 recept or gene and no homozygotes for this variant were observed by any group . However, an excess of homozygotes for both alleles of the DRD3 polym orphism was observed in schizophrenic patients (chi(2) = 8.54, P = 0.0 03, odds ratio = 1.64, 95% CI = 1.18-2.29). We also observed a signifi cant excess of the 1-1 (Ser9Ser) genotype (chi(2) = 8.13, P = 0.004, o dds ratio = 1.7, 95% CI = 1.18-2.4), No evidence of heterogeneity betw een samples was detected and there was no evidence of an allelic assoc iation, These findings suggest that the rare Cys311 variant in exon 7 of the DRD2 receptor gene does not play a role in the pathogenesis of schizophrenia in European populations, Currently, our results do suppo rt the previous findings of an association between increased homozygos ity of the Ser/Gly variant of the Dopamine D3 receptor gene and schizo phrenia. (C) 1998 Wiley-Liss, Inc.