The Frequency of Certain Genetic Polymorphisms and Their Influence on the Therapeutic Response of Patients Treated with Olanzapine

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Abstract Olanzapine is an atypical antipsychotic that serves as the first line of schizophrenia treatment. The metabolism of olanzapine takes place with the leading participation of two enzymes, CYP1A2 and CYP2D6. The CYP450 enzyme activity can be changed under the influence of many drugs, which results in potentially significant interactions in which one drug can increase the toxicity (inhibition of cytochrome) or reduce the second drug's therapeutic effect. The aim of this study was to examine the frequency of certain genetic polymorphisms and their impact on the therapeutic response of patients treated with olanzapine. This research was conducted according to the design of a prospective, interventional, clinical study of phase IV by type of case series, where the stratification of the subjects was performed according to the obtained types of tested genotypes. Patients (N=120) were recruited at the Clinic of Psychiatry, University Clinical Center Kragujevac, in Serbia. The primary endpoint to assess the therapeutic response in this study was PANSS. In our study, the presence of the investigated gene variations (UGT1A4, CYP1A2, FMO3, and CYP2D6) does not affect the clinical response to olanzapine therapy in patients suffering from schizophrenia, compared to patients who are carriers of the wild-type gene. The presence of genes of CYP1A2*1C (rs2069514, −3860G>A), CYP1A2 (rs2472297, 74735539C>T), FMO3 E158K (rs2266782, 15167G>A), FMO3 V257M (rs1736557, 18281G>A), FMO3 E308G (rs2266780, 21443A>G), CYP2D6*3 (rs35742686, 2549delA), CYP2D6*4 (rs3892097, 1846G>A), CYP2D6*6 (rs5030655, 1707delT) does not change the clinical response to olanzapine therapy in patients suffering from schizophrenia, compared to patients who are carriers of the wild-type gene.