EXAMINATION OF NEW AND REPORTED DATA OF THE DRD3 MSCL POLYMORPHISM - NO SUPPORT FOR THE PROPOSED ASSOCIATION WITH SCHIZOPHRENIA/

The dopamine D3 (DRD3) receptor gene has been implicated in the aetiol ogy of schizophrenia as a candidate gene since it combines both the do pamine receptor and limbic hypotheses of the disease. Previous associa tion studies of a DRD3/MscI polymorphism suggested an increased freque ncy of homozygosity at the DRD3 receptor gene in schizophrenia. Homozy gosity appeared to be particularly frequent in male patients, individu als with family history of the disease and in good responders to neuro leptic treatment. Many studies have since examined this polymorphism a nd have altered or extended the original homozygosity hypothesis. In t his study, we have investigated the distribution of the DRD3/MscI poly morphism in 198 Irish schizophrenic patients and 235 ethnically matche d controls. Patients and controls showed similar allele and genotype f requencies. Furthermore, linkage analysis using two microsatellite mar kers flanking the DRD3 gene was performed on 265 Irish schizophrenic f amilies, with substantially negative results. Our findings, in combina tion with a review of previous studies do not support a role for the D RD3/MscI polymorphism in the pathogenesis of schizophrenia.