Single nucleotide polymorphisms and clozapine response in Korean schizophrenic patients who are refractory or intolerant to conventional antipsychotic agents

Abstract

Background and Purpose: Clozapine has a regulatory effect on D2 and serotonergic receptors. Its antagonistic effect on 5-HT2 receptors improves the negative symptoms of schizophrenia. Clozapine is recommended for patients who are intolerant to other antipsychotic agents. The mechanism of clozapine response in schizophrenic patients is still completely unknown; it is proposed that the dopamine D2 receptor gene and the serotonergic receptor gene may be responsible. Schizophrenia is accompanied by multiple genetic alterations, including single nucleotide polymorphisms. The association between D2 receptors and clozapine response in schizophrenic patients has been studied in other ethnical groups, including Caucasians. The identification of polymorphisms spanning the dopamine D2 receptor gene (DRD2) connected with clozapine treatment response in intolerant schizophrenic patients might be helpful in selecting patients for clozapine treatment. The present study aimed to investigate the effect of single nucleotide polymorphisms (SNPs) spanning the entire dopamine D2 receptor gene on clozapine response in schizophrenic patients intolerant to conventional antipsychotics. Methods: We divided patients with schizophrenia into two groups according to the presence of psychotic symptoms. The severity of their symoptoms was measured using the Brief Psychiatric Rating Scale (BPRS). Using fluorescence assay, the following 12 SNPs of DRD2 (going from 5< to