A dopamine D2 receptor gene-related polymorphism is associated with schizophrenia in a Spanish population isolate

Numerous lines of evidence have highlighted the involvement of the dopamine system in the pathophysiology of schizophrenia. Association studies of dopaminergic genes such as the dopamine D2 receptor gene (DRD2), however, have produced contradictory results. To test the hypothesis that DRD2polymorphisms are associated with schizophrenia, we investigated two DRD2-related polymorphisms (TaqI A1A2 or rs1800497 and –141-C InsDelor rs1799732) in a Spanish population isolate from northern Spain consisting of 165 controls and 119 patients with schizophrenia. The TaqI A1 allele was less frequent in schizophrenic patients than in controls (P0.002). A similar association was found for the TaqI A2A2 genotype (P0.0003). No association was found for the DRD2−141-C InsDelpolymorphism. The strong association between a potentially functional polymorphism, downstream of the DRD2gene and schizophrenia, suggests that the direct or indirect functional effects of this polymorphism, acting on either the ANKK1or DRD2genes, may play a role in the pathophysiology of schizophrenia.