The effect of polymorphism on serotonin and histamine reseptor in antipsychotic action of olanzapine

Abstract

Purpose There are individual differences in the effects of antipsychotic drugs. As the genetic polymorphisms of several reseptors are thought to be a cause of individual differences, we investigated the effects of the genetic polymorphisms in serotonin receptors, histamine receptor and serotonin transporter genes on the clinical outcome of olanzapine. Methods: Patients of schizophrenia were enrolled simultaneously at St. Marianna University hospital with their written informed consent. In this study was approved by the institutional review board at St. Marianna University School of Medicine. Patients were given olanzapine (5~20mg) and blood were collected at 8weeks after drug administration. Clinical symptoms were evaluated by the PANSS scores before drug administration and at 4~8weeks of follow up. Genomic DNA were extracted from peripheral blood samples to analyze genetic polymorphisms 5HT2A (25Thr/Asp, 102T/C, 452His/Tyr, ‐1438G/A), 5HT2C (23Cys/Ser), 5HTTLPR (‐1396 44bp Ins/Del), H2R (‐1018G/A), by PCR‐RFLP and the method of direct sequence. Results: The polymorphic groups of 5HT2A (452His/Tyr, ‐1438G/A) and 5HT2C (23Cys/Ser) were prone to present better PANSS scores compared to the wild type group, whereas the group of 5HT2A(102T/C) showed insignificant results. It is necessary to analyze more number of cases. Clinical Pharmacology & Therapeutics (2004) 75, P18–P18; doi: