Introduction: The dopamine transporter (DAT) and dopamine receptors play a pivotal role in dopaminergic neurotransmission. The association of DAT gene variable number tandem repeat (VNTR) and Dopamin D3 receptor (DRD3) Ser9Gly polymorphisms and schizophrenia and antipsychotic response were studied before [1]. The Ser9Gly polymorphism of DRD3 receptor has been found to be associated with general susceptibility to schizophrenia. Negative studies have also been published, querying the relevance of the Ser9Gly polymorphism in schizophrenia. The majority of data on the VNTR polymorphism of the DAT seem to be consistent, suggesting no association with schizophrenia. Studies on association of these genes with antipsychotic drug response were also conflicting. Some studies revealed an association between these polymorphisms and response to antipsychotics and others do not [2,3]. We aimed to investigate the effects of DRD3 gene and DAT gene polymorphisms on schizophrenia and olanzapine response.
Methods: Our study comprised 95 unrelated subjects who strictly met DSM-IV criteria for schizophrenia and 186 controls and all were of Turkish origin. All patients were evaluated with SAPS, SANS and BPRS at the beginning of the study and at the end of six weeks. Patients were taking olanzapine 5−30 mg/day. Blood for DNA analysis were obtained and analyzed as mentioned in literature. SPSS 13.0 program was used for evaluation of data.
Results: 45 patients had ser/ser (%47.9), 37 patients had ser/gly (%39.4) and 13 patients had gly/gly (%12.8) polymorphism of DRD3 gene. 82 of the controls had ser/ser (%44.1), 85 of controls had ser/gly (%45.7) and 19 of controls had gly/gly (%10.2) polymorphism of DRD3 gene. 27 patients had 9/10 (%28.4), 56 patients had 10/10 (%58.9), 4 patients had 10/11 (%4.2), 7 patients had 9/9 (%7.4) and 1 patient had 6/9 (%1.1) tandem repeat polymorphism of DAT gene. 55 of controls had 9/10 (%44.7), 56 of controls had 10/10 (%45.5), 5 of controls had 10/11 (%4.1), 2 of controls had 9/9 (%1.6) and 2 of them had 6/9 (%1.6) tandem
repeat polymorphism of DAT gene. No association was found between DAT gene VNTR and DRD3 Ser9Gly polymorphisms and schizophrenia. We also couldn’t find statically significant
association between response to olanzapine and DAT and DRD3 polymorphisms.
Conclusion: Recent studies have focused on the Ser9Gly polymorphism of the DRD3 gene and VNTR polymorphism of DAT gene but the results were inconclusive. DRD3 Ser9Gly polymorphism was associated with response to clozapine and risperidone. Some of the studies were mentioning that Ser9Gly polymorphism of the DRD3 gene was associated with response to negative symptoms [2,3]. Our study findings couldn’t Show an association between schizophrenia and olanzapine response with these polymorphisms. Despite our negative result, Ser9Gly polymorphism of the DRD3 gene and VNTR polymorphism of DAT gene might be a useful genetic marker but there is a need of studies with larger samples and longer duration.