Differences in MDR1 (C3435T), CYP2D6, and CYP1A2 Genotype Frequencies between Patients with Treatment Failure to Antipsychotics and Healthy Russian Population

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Author(s): Tatiana Zhiganova * , Eugenia Radkova , Tatiana Sergeeva , Victoriia Volovnikova .

Journal Name: Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics)

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Background: Personalized approach is one of the options to overcome treatment failure in psychiatry and increase efficacy of antipsychotic treatment for an individual patient by using genetic tests.

Objective: The aim of this study was to investigate the frequency of MDR1 (C3445T), CYP2D6, CYP2C19, and CYP1A2 genotypes in psychiatric patients with treatment failure to antipsychotics to compare the results with those published for the Russian population.

Methods: A total number of 52 patients attending a psychiatry outpatient clinic were included in the study. All patients required changing the therapy with antipsychotics due to treatment failure.

Results: We revealed the higher frequency of Т/Т MDR1 (C3435T) homozygotes among study patients as compared with the Russian healthy population. For CYP1A2, the higher frequency of normal metabolizers (*1A/*1A) and lower frequency of slow metabolizers (*1F/*1F) were observed. No difference was found for intermediate metabolizers (*1A/*1F) and one patient had *1A/*1C genotype with decreased activity. For the majority of CYP2D6 genotypes the observed frequencies were similar to those reported for the Russian healthy population except for CYP2D6 *3/*4 (slow metabolizers), for which higher frequency among study patients was found. The frequencies of CYP2С19 genotypes were comparable to the Russian population, however no slow metabolizers (*2/*2, *2/*3, *3/*3 genotypes) were identified.

Conclusion: Psychiatric patients with treatment failure to antipsychotics demonstrated high frequency of T/T MDR1 (C3435T) and CYP2D6 *3/*4 genotypes coding inactive proteins. The frequency of CYP1A2 wild type genotype *A/*A was higher with simultaneous decrease in the frequency of *F/*F genotype compared with healthy Russian population. Further studies of MDR1 (C3435T) genotype as well as CYP2D6, CYP2C19, and CYP1A2 genotypes frequency should be conducted in patients with treatment failure to antipsychotics.

Keywords: Pharmacogenetics, antipsychotics, MDR1, cytochrome system, CYP2D6, CYP2C19, CYP1A2.

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(E-pub Ahead of Print)
DOI: 10.2174/1875692117666190724141831