Association Study Between The Dopamine D₃ Receptor Gene Polymorphisms And Antipsychotic Response

The dopamine D3 receptor (DRD3) is a G protein-coupled receptor that belongs to the dopamine D2-like receptor family. It is preferentially expressed in limbic regions that are associated with cognitive and emotional functions. Previous neurochemical and anatomical investigations have suggested a role for DRD3 in the pathology of schizophrenia. Also, pharmacological studies have shown that many antipsychotic drugs exhibit a high affinity for DRD3. These lines of evidence implicate a role of this receptor as an important target for antipsychotic drugs. Risperidone is an effective first-line atypical antipsychotic agent. Recent studies have reported an association of the Ser9Gly polymorphism in the DRD3 gene with therapeutic response to risperidone, but the results were inconsistent. To further evaluate the role of genetic variations within the DRD3 gene in antipsychotic action, we conducted a detailed association study of the DRD3 gene with risperidone response.The present study genotyped eight single nucleotide polymorphisms (SNPs) distributed throughout the DRD3 gene by direct DNA sequencing and examined five of these for association with risperidone efficacy, following an eight-week period of risperidone monotherapy in one hundred and thirty Chinese Han schizophrenic patients. Clinical symptoms were assessed before and after the treatment period, using the Brief Psychiatry Rating Scale (BPRS). Given the possible influences of non-genetic factors on symptom improvement, the confounding effects of the clinical parameters were estimated and the baseline BPRS score closely correlated with risperidone efficacy was included as a covariate for the association analyses. Neither was any significant association observed between the five polymorphisms and improvement in total BPRS scores, nor was any significant discrepancy of haplotype frequencies detected between responder and non-responder groups.The current results indicate that genetic variations within the DRD3 gene may not greatly affect the therapeutic efficacy of risperidone for the mainland Chinese population, and thus not contribute significantly to inter-individual variability in the risperidone response.