engleski

The association study of polymorphisms DRDd2, SLC6A3 and COMT genes and achieving the symptomatic remission in male schizophrenic patients treated with olanzapine

INTRODUCTION: Olanzapine is one of the most prescribed second generation antipsychotic used in the treatment of schizophrenia. Along with other factors, variations in treatment response among patients with schizophrenia could be genetically predetermined. The aim of this study was to investigate the association between functional polymorphic gene variants of dopamine receptor type 2 (DRD2), dopamine transporter (SLC6A3, DAT1), and catechol-O-methyltransferase enzyme (COMT), and treatment response to olanzapine and achieving the symptomatic remission in schizophrenic patients. MATERIALS AND METHODS: The study included 150 male schizophrenic patients treated with olanzapine (5-20 mg/d) during the period of four years. The severity of symptoms, treatment response and achieving symptomatic remission for 6 months were assessed using the PANSS scale. Genotyping of DRD2 (rs1800497, Taq1A) and SLC6A3 (rs28363170, DAT1 VNTR) was performed by PCR-RFLP and PCR, while COMT (rs4680, Val158Met) was genotyped by real-time PCR analysis. RESULTS: 45 (31%) participants achieved criteria for symptomatic remission. A statistically significant association was found between COMT Val158Met polymorphism and achieving symptomatic remission. Patients with COMT Val/Met genotype had more than three times greater odds to achieve symptomatic remission compared to other COMT genotypes (OR = 3.3, 95% CI = 1.14 to 9.32). There was no statistically significant association between genotype and allele frequencies of DRD2 and SLC6A3 and achieving symptomatic remission. CONCLUSIONS: Although mechanisms are still incompletely understood, this study confirms the role of genetic factors and predictive value of COMT Val158Met polymorphism for treatment response to olanzapine and achieving symptomatic remission criteria in patients with schizophrenia.

Schizophrenia; DRD2; COMT; DAT gene polymorphisms; olanzapine

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