Frequencies of ABCB1 Gene Variant Alleles and Their Role in Response to Antipsychotic Therapy in Patients with Schizophrenia Spectrum Disorders: Narrative Review

Abstract

The ABCB1 transporter protein (also known as P-glycoprotein, P-gp) plays a crucial role in the pharmacokinetics of antipsychotics (APs), determining their bioavailability and distribution in the body. The ABCB1 genetic polymorphisms significantly contributes to interindividual dif-ferences in response to AP therapy in patients with schizophrenia spectrum disorders (SSDs). Increased P-gp functional activity is associated with the development of pseudoresistance to APs, while decreased activity is linked to the development of AP-induced adverse drug reactions. This review aims to systematize current data on the population frequencies of ABCB1 gene allelic variants that influence the activity of P-gp and to establish a scientific foundation for the devel-opment of domestic, ethnically-oriented pharmacogenetic diagnostic test systems. A search was conducted in the databases PubMed, eLIBRARY.RU, Google Scholar, PharmGKB, DrugBank, the Geography of Genetic Variants Browser, ClinVar, dbSNP, SNPedia, Drugs@FDA, Russian State Register of Medicines, the Database of Population Frequencies of Genetic Variants in the Russian Population, the RUSeq Browser, The Rubricator of Clinical Recommendations. Available data on the population frequencies of the most extensively studied high-function (n = 5), low-function (n = 15), and loss-of-function (n = 5) allelic variants of the ABCB1 gene were retrieved and analyzed. The frequency of variant alleles of the ABCB1 gene is heterogeneous across different global populations, a critical factor to consider in the development of pharmacogenetic diagnostic test systems. The ethno-territorial heterogeneity of the Russian gene pool necessitates the develop-ment and subsequent validation of local (region-specific) pharmacogenetic diagnostic test sys-tems, based on large-scale population studies conducted within specific administrative-territorial units.