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No. 2 (2026)

GENERAL THERAPY QUESTIONS AND REVIEWS

Influence of Single-Nucleotide Variants of the ABCB1 Gene on the Efflux of Antipsychotics in Patients with Schizophrenia Spectrum Disorders (Review)

https://doi.org/10.48612/psyph/f215-71p5-phkz

Published 2026-06-30

  • N.A. Shnayder
    • ,
  • A.A. Abramenko
    • ,
  • E.I. Glushchenko
    • ,
  • E.K. Kaisinova
    • ,
  • A.M. Shirukova
    • ,
  • I.R. Boyko
    • ,
  • N.G. Neznanov
    • ,
  • R.F. Nasyrova

N.A. Shnayder
Bekhterev National Medical Research Center for Psychiatry and Neurology; Molecular and Cell Technologies; Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

A.A. Abramenko
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology

E.I. Glushchenko
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology

E.K. Kaisinova
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology

A.M. Shirukova
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology

I.R. Boyko
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology

N.G. Neznanov
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology

R.F. Nasyrova
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology

Abstract

A comprehensive analysis of the role of single nucleotide variants (SNVs) of the ABCB1 gene, encoding the efflux transporter P-glycoprotein (P-gp), involved in the removal of antipsychotics (APs) from the brain into the blood, is important for assessing interindividual differences in therapeutic response. Understanding the molecular basis of resistance to APs and adverse drug reactions (ADRs) is a necessary step toward a personalized approach to the treatment of schizophrenia spectrum disorders (SSDs). To update information about the role of SNVs of the ABCB1 gene and their contribution to interindividual differences in AP response in patients with SSDs. The aim of this descriptive review was a search of full-text publications in Russian and English in eLIBRARY.RU, PubMed, and Google Scholar databases for the period 2020-2025. Publicly available international bioinformatics databases Genokarta, SNPedia, NCBI Gene, and UniProt were used as sources of information on the structure of the ABCB1 gene and the main characteristics of SNVs. A total of 24 SNVs of the ABCB1 gene were presented, including: 4 highly functional (rs1882478, rs2235047, rs2235048, and rs6949448); 15 low-functional (rs9282564, rs10280101, rs1128503, rs1202186, rs2032583, rs2091766, rs12720067, rs2235035, rs2235040, rs2235046, rs2235067, rs3789243, rs4148739, rs4148740 and rs7787082); 4 non-functional (rs1045642, rs2235015, rs10248420 and rs11983225); 1 SNV (rs2032582), the effect of which on the functional activity of P-gp (increase or decrease) depends on the variable allele. Variable alleles of some SNVs of the ABCB1 gene may play a significant role in shaping interindividual differences in response to APs in patients with SSDs, but so far clinical significance has been shown only for the four most studied non-functional and low-functional SNVs rs1045642, rs1128503, rs2032582, rs2235048.

Keywords

pharmacogenetics, antipsychotic, ABCB1 gene, minor allele, single-nucleotide variant, genetic polymorphism, transport protein, P-glycoprotein, antipsychotic efflux, therapeutic resistance, neurotoxicity, pharmacogenetic testing

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