This article investigates the factors hindering the widespread implementation of pharmacogenetic tests into routine clinical practice. Based on an analysis of international and Russian physician surveys (ESC, 2026; Russian surveys 2022–2025), the main barriers to the broad adoption of pharmacogenetic testing are examined. It is shown that despite a high level of physician readiness to use pharmacogenetic tests (up to 73 % of respondents), only one-third of specialists have actual access to them. Three key groups of problems are identified: a lack of knowledge and skills for result interpretation; insufficient infrastructure (high cost, long turnaround times, lack of standardization); and the absence of mandatory provisions in clinical guidelines. Overcoming these barriers requires a comprehensive approach, including improving the regulatory framework, training healthcare professionals, enhancing infrastructure, and providing economic justification.

Relevance. The study of the prevalence of ABCB1 polymorphic markers and the prediction of clinical, laboratory and demographic parameters in patients with ischemic stroke is a relevant area of pharmacogenetics and practical neurology.
Objective. To determine the frequency of ABCB1 polymorphism (C3435T, rs1045642) in patients with ischemic stroke and evaluate its association with clinical, laboratory and demographic parameters of patients.

Material and methods. The study group included 120 patients with non-cardioembolic ischemic stroke. Genotyping of ABCB1 polymorphisms (C3435T, rs1045642) was performed by polymerase chain reaction. An analysis of clinical and demographic factors and distribution frequencies of ABCB1 genotypes (C3435T) was performed.

Results. The CC genotype was verified in 18.0 %, CT in 56.0 %, and TT in 26.0 % of patients. The distribution of ABCB1 genotypes (C3435T, rs1045642) among patients with ischemic stroke complied with the Hardy-Weinberg law (χ²=1.81; p=0.18). When assessing the comparability of clinical and demographic characteristics and the results of genotyping for ABCB1 (C3435T, rs1045642), a statistically significant difference in the frequency of detection of diabetes mellitus and overweight in patients with ischemic stroke was noted. Diabetes mellitus and obesity were detected with a higher frequency in the group of patients carrying the CT+TT genotypes: in the presence of diabetes mellitus — 31.6 % versus 18.2 % (p=0.023); in the presence of excess body weight — 36.7 % versus 18.2 % (p=0.003). No statistically significant association with the clinical features of the course of ischemic stroke was found. Also, no characteristic differences were found between patients carrying the CT/TT genotypes (those who responded and those who did not respond to antiplatelet therapy with clopidogrel). When assessing the comparability of average quantitative laboratory parameters in carriers of the CC and CT+TT genotypes of the ABCB1 polymorphism (C3435T, rs1045642), it was revealed that in the general blood test, the average level of leukocytes and neutrophils was statistically significantly higher in the group of patients with the CC genotype.

Conclusion. The obtained data may influence the choice of priority for the implementation of pharmacogenetic tests both in cerebrovascular pathology and in other diseases.

Background. Prescription of dangerous and undesirable drug combinations occurs in healthcare systems of most countries worldwide. Among drugs with the highest risk in such combinations, statins are considered particularly hazardous due to their significant metabolic activity. In the healthcare system of Kazakhstan, this problem remains poorly studied, and the structure of genetic predisposition to adverse effects is unknown.

Objective. To determine the frequency of SLCO1B1 gene polymorphism in patients with coronary artery disease of the Kazakh population of East Kazakhstan and its association with the efficacy and safety of atorvastatin therapy.

Methods. A cross-sectional clinical-genetic study was conducted. The study did not involve any active intervention in the ongoing treatment of patients prescribed by physicians. Medical records containing prescription data from inpatient and outpatient settings were analysed. The presence of SLCO1B1 (c. 521T>C) polymorphisms of the OATP1B1 transporter protein was assessed.

Results. The study included 178 individuals (108 men and 70 women) aged 40 to 70 years (mean age 61.1±7.8 years). All patients were of Kazakh ethnicity. In the examined group of patients receiving statin therapy, a significant frequency of genetic variants associated with an increased risk of statin-related complications was identified. Significant differences in the frequency of clinical manifestations of drug-induced muscle adverse effects were observed for the SLCO1B1 gene in carriers of the homozygous CC genotype (χ² = 23.31, p < 0.001). A marked increase in creatine phosphokinase activity (3.39-fold, p < 0.001) and a reduction in atorvastatin efficacy were also observed.

Conclusions. In the studied Kazakh population, analysis of the SLCO1B1 (c. 521T>C) polymorphism can be recommended as a genetic marker of the risk of adverse reactions during lipid-lowering therapy with statins (atorvastatin), as this polymorphism reduces treatment efficacy and increases the risk of side effects.

Relevance. Despite the use of antipsychotic drugs is still one of the most effective treatment methods of schizophrenia, the 20–30 % of patients do not respond adequately to pharmacotherapy. This inefficacy may stem from genetic variability, which influences drug metabolism, adverse reactions, and treatment response, alongside gene-environment interactions. This study aimed to investigate the association between polymorphic gene loci and pharmacoresistant schizophrenia among Belarusian patients.

Objective. To study the relationship of a number of polymorphic gene loci with pharmacoresistance (FR) in patients with schizophrenia, residents of Belarus.

Methods. The study included 161 people with schizophrenia. The main group included 104 patients with no improvement when treating with two or more antipsychotics (including an atypical antipsychotic) for 6 to 8 weeks; the comparison group included 57 patients with positive response to pharmacological treatment of schizophrenia. Pharmacogenetic testing was performed using standard methods of nucleic acid isolation and PCR analysis. 19 polymorphic loci in 15 genes (CYP2D6, CYP2C9, CYP2C19, CYP1A2; MDR1, ANKK1, HTR1A, HTR2A, SLC6A4, HTR2C, COMT, MAOA, BDNF,

DRD2, UGT1A1) were genotyped. Statistical processing of clinical and genotyping data was carried out using the SPSS Statistics 20.0 program. The odds ratio (OR) and 95 % confidence interval (CI) were used as an indicator of the relationship between alleles and genotypes with the risk of developing PR.

Results. Comparison of the genotypes and alleles frequencies in the studied groups of patients with schizophrenia revealed an association of PR in carriers of alleles — A (CYP2D6, rs3892097) (χ²=4.124; p=0.042), G (COMT, rs4680) (χ²=9.006; p=0.003); AG genotype (CYP2D6, rs3892097) (χ²=6,647; р=0,01), CC genotype (HTR1A, rs6295) (χ²=5.522; p=0.019). Further analysis revealed an increase in the risk of PR when these alleles were combined with other gene loci. Patients with pharmacogenetic profiles A-/A(CYP2D6 / CYP1A2), (OR 2.926; CI 1.206–7.102); A-/B-/T(CYP2D6 / CYP1A2 / MDR1), (OR 4.833) had an increased risk of developing FR; CI 1,753–13,328); G-/L(COMT / SLC6A4), (OR 3,172; CI 1,500–6,709); G-/LL (COMT / SLC6A4), (OR 6,923; CI 1,900–25,227); G-/LL/T(COMT / SLC6A4 / MDR1), (OR =11.143; CI 2.415–51.414); CC/T(HTR1A / MDR1), (OR 2.564; CI 1.120–5.873).

Conclusion. A study using pharmacogenetic testing of residents of Belarus with schizophrenia revealed a significant association of the risk of PR with polymorphic loci of the genes CYP2D6 (rs3892097), HTR1A (rs6295), COMT (rs4680). An increased risk of PR was observed when the identified alleles were combined with polymorphic loci of the CYP1A2 (rs762551), MDR1 (rs1045642), and SLC6A4 (5-HTTLPR) genes. Pharmacogenetic risk profiles for the development of PR during antipsychotic therapy in patients with schizophrenia are described.

Background. According to Russian and European clinical guidelines, methotrexate (MTX) is used for initial therapy of rheumatoid arthritis (RA), under regular medical and laboratory monitoring to prevent adverse reactions (AE). The incidence of AEs in MT reaches 72.9 %, with gastrointestinal reactions (20–30 %), hepatotoxicity (10–15 %), and hematological disorders (5–10 %) predominating. Hepatotoxicity requires long-term monitoring of liver function according to DILIN recommendations, while pulmonary complications (1–2 %) require immediate discontinuation of therapy. Polymorphisms of MT metabolism genes (ABCB1, SLC19A1, FPGS, GGH, ATIC, MTHFR, DHFR), by altering its pharmacokinetics and pharmacodynamics, determine individual tolerability of the drug. Pharmacogenetic testing enables the development of personalized approaches to RA therapy, reducing the risk of MT discontinuation and switching to expensive biologics.

Objective. To develop a pharmacogenetic model for predicting the risk of developing PD MT in patients with RA based on gene polymorphisms of key proteins involved in methotrexate metabolism.

Methods. The study included 294 patients with a confirmed diagnosis of RA who received MT monotherapy for 6 months. The associations between single-nucleotide polymorphisms (SNPs) of nine genes involved in MT metabolism and transport (ABCB1, ADA, AMPD1, ATIC, FPGS, GGH, ITPA, MTHFR, SLC19A1) and the development of PD were studied. Genotyping was performed by polymerase chain reaction (PCR) using domestically produced kits. A comprehensive statistical analysis was performed using multivariate dimensionality reduction (MDR) with 10-fold cross-validation, sensitivity and specificity assessment, and entropy analysis to identify epistatic gene interactions.

Results. PDs were recorded in 82 patients (27.9 %), primarily hepatotoxicity (17 %). Primary automated models involving 1–3 genes demonstrated low reliability, while data-driven models considering the biological role of genes demonstrated high predictive value. Five-gene and six-gene models, including polymorphisms of the transport systems (SLC19A1, ABCB1), polyglutamation (GGH, FPGS), and adenosine pathway (ATIC), proved optimal, with a maximum sensitivity of 91.5 % and specificity of 69.3 %.

Conclusion. A combined analysis of gene polymorphisms involved in MT transport and metabolism significantly improves the accuracy of predicting MT tolerance in patients with RA. A six-gene model combining the SLC19A1, ABCB1, GGH, FPGS, and ATIC genes demonstrated the greatest diagnostic value. The developed "if — then" predictive rule enables a personalized approach to therapy and can be used in clinical practice to predict the risk of MT-related PD.

Objective. The study aimed to assess pharmacogenetic characteristics of prescribed versus taken pharmacotherapy in patients with cardiovascular diseases (CVD).

Materials and methods. A total of 813 electronic health records (EHRs) were selected from available electronic medical documents (n=8791) of CVD patients, using probability cluster sampling method. Unstructured text from the EHRs (n=813) was used to create a database characterizing gender, age, ICD-10 codes, prescribed and taken pharmacotherapy, international nonproprietary names (INNs), and pharmacogenes corresponding to each case of pharmacotherapy. Pharmacogenetic drugs and associated pharmacogenes were identified using database ClinPGx.org.

Results. Patients aged 62 years (IQR 56–68 years); 70.2 % men. The list of prescribed drugs comprised 347 INNs; the list of taken drugs comprised 253 INNs; both lists comprised 435 INNs, suggesting a mismatch between the lists. Numbers of INNs per document ranged from 1 to 23 for taken drugs (Me=6, IQR 3–9; n=385) and from 1 to 20 for prescribed drugs (Me=6, IQR 4–9; n=724), p > 0.05. The study identified 1120 pharmacogenes. Number of associated pharmacogenes per INN did not significantly differ between the lists of prescribed and taken drugs (1, IQR 0–7). However, the differences were found between the incidence rates of individual pharmacogenes. Pharmacogenes UGT1A9, UGT1A3, AGTR1, KIF6, and SCAP were significantly more often associated with prescribed drugs (p <0.05); ABCB1, NOS3, GNB3, ADRB1, and ADD1 were significantly more often associated with taken drugs (p <0.05).

Conclusion. The study demonstrated a mismatch between the pharmacogenetic profiles of prescribed versus taken pharmacotherapy in CVD. Drug-gene interactions may affect treatment adherence.