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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.

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2363-8915
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Volume 31, Issue 4

Issues

1846G>A polymorphism of CYP2D6 gene and extrapyramidal side effects during antipsychotic therapy among Russians and Tatars: a pilot study

Dmitriy A. Sychev
  • Department of Clinical Pharmacology, Russian Medical Academy of Postgraduate Education, Moscow, Russian Federation
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Irina S. Burashnikova
  • Corresponding author
  • Department of Clinical Pharmacology and Pharmacotherapy, Kazan State Medical Academy, Moushtari, 11, Kazan 420012, Russian Federation, Phone: +79047604240, Fax: +7 843 2730802
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ruslan E. Kazakov
  • Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-11-22 | DOI: https://doi.org/10.1515/dmpt-2016-0027

Abstract

Background:

Сytochrome P450 CYP2D6 activity affects antipsychotic therapy safety. 1846G>A (CYP2D6*4) polymorphism frequency varies among different ethnic groups.

Methods:

We studied 1846G>A polymorphism in Tatar and Russian schizophrenic patients taking different antipsychotics and association of 1846G>A polymorphism and extrapyramidal disorders (EPD) frequency in schizophrenic patients on haloperidol monotherapy in daily doses up to 20 mg.

Results:

Heterozygous 1846GA genotype frequency among Tatars was lower (23.8% vs. 32.4% in Russians), but the differences did not reach statistical significance. The 1846A allele frequency among Tatars was also lower (11.9% vs. 24.3% in Russians), but the difference was not quite significant (p=0.0592). Average daily haloperidol dose in the group without EPD was significantly higher than in the group with EPD (11.35±4.6 vs. 13.87±3.3 mg, p=0.0252), but average daily haloperidol dose/weight ratios in the compared groups had no significant differences. A statistically significant association between EPD development and heterozygous 1846GA genotype and 1846A allele carrier frequency was revealed among all schizophrenic patients and among those of Tatars.

Conclusions:

Further well-designed pharmacogenetic studies in different Russian regions are needed to improve psychotropic therapy safety and to establish evidence-based indications for pharmacogenetic testing in clinical practice.

Keywords: 1846G>A (CYP2D6*4) polymorphism; antipsychotic; biotransformation; ethnic differences of 1846A allele carrier frequency; extrapyramidal side effect/disorder; pharmacogenetics; Russians; schizophrenia; Tatars

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About the article

Received: 2016-08-05

Accepted: 2016-10-20

Published Online: 2016-11-22

Published in Print: 2016-12-01


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. I.S.B. conceived the idea of this study, participated in its design, collected the data, performed the analysis and wrote the initial draft of the manuscript. D.A.S. participated in the conception and design of the study, contributed to the analysis and helped to prepare the draft manuscript. R.E.K. participated in the conception and design of the study, performed genotyping and helped to prepare the draft manuscript.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Drug Metabolism and Personalized Therapy, Volume 31, Issue 4, Pages 205–212, ISSN (Online) 2363-8915, ISSN (Print) 2363-8907, DOI: https://doi.org/10.1515/dmpt-2016-0027.

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