Pilot study of the G-protein beta3 subunit gene (C825T) polymorphism and clinical response to Olanzapine or Olanzapine-related weight gain persons with schizophrenia

Background: Despite advances in schizophrenia treatment, nearly 30% of patients do not respond to atypical antipsychotic agents, such as olanzapine. Furthermore, 30-60% of patients will gain significant weight during the course of olanzapine therapy. Little research has been done to investigate the relationship between antipsychotic treatment outcomes and genetic variability in second messengers coupled to serotonin (5HT) receptors. The purpose of this investigation was examine associations between the second messenger G-Protein Beta3 Subunit Gene (GNB3) C825T polymorphism and olanzapine response and weight gain treatment. Material/Methods: We conducted a pharmacogenetic association study to examine GNB3 genotypes in relation to olanzapine clinical response (as measured by the Brief Psychiatric Rating Scale or Scale for the Assessment of Negative Symptoms) or weight gain. Subjects included forty-two individuals meeting DSM-IV criteria for schizophrenia that started olanzapine, were titrated to a fixed dose for 6 weeks, and subsequently genotyped for this investigation. Results: No statistically significant associations existed between our outcome variables and GNB3 genotypes. However we did observe trends suggesting a potential relationship between the TT genotype, response, and weight gain that warrant further investigation. Conclusions: Preliminary results showed no statistical relationship between the C825T polymorphism and olanzapine response or weight gain. Numerical differences in outcome measures between the TT vs. CT/CC genotype groups indicate that G-protein second messenger systems variability coupled to primary targets of atypical antipsychotics may relate to clinical outcomes in persons with schizophrenia and that future research in this area is warranted.