Background. Helicobacter pylori infection is a major risk factor for gastric cancer, and its eradication is considered a primary preventive measure. Proton pump inhibitors (PPIs) are a cornerstone of eradication therapy, but their efficacy is significantly influenced by genetic polymorphisms in the CYP2C19 enzyme, which is responsible for their metabolism.

Objective. To summarize and present current research on the impact of CYP2C19 genetic polymorphism on the effectiveness of H. pylori eradication therapy.

Materials and methods. A literature review was conducted using Russian and international databases (RSCI, PubMed, ResearchGate) with keywords including "CYP2C19 polymorphism," "proton pump inhibitor metabolism," and "Helicobacter pylori eradication." A total of 41 publications most relevant to the topic were analyzed.

Results. The metabolism of first-generation PPIs (omeprazole, lansoprazole, pantoprazole) is highly dependent on CYP2C19 activity. Patients are classified into different metabolic phenotypes (ultrarapid – UM, rapid – RM, normal – NM, intermediate – IM, poor – PM) based on their CYP2C19 genotype. Evidence, primarily from Asian populations, indicates that NM and RM/UM phenotypes are associated with lower eradication rates due to accelerated PPI metabolism and reduced drug exposure, whereas IM and PM phenotypes show higher efficacy. The Russian population has a high frequency of the rapid metabolizer allele CYP2C19*17, suggesting potential suboptimal response to standard PPI doses. Rabeprazole and esomeprazole demonstrate less dependence on CYP2C19, leading to more consistent efficacy across different genotypes. Clinical guidelines (e.g., CPIC, DPWG) recommend genotype-guided PPI dosing to optimize therapy.

Conclusion. CYP2C19 genetic polymorphism is a critical determinant of PPI pharmacokinetics and the effectiveness of H. pylori eradication. Pharmacogenetic testing for CYP2C19 can be a valuable tool for personalizing anti-Helicobacter therapy, particularly in populations with a high prevalence of rapid metabolizer alleles, by enabling the selection of the most appropriate PPI and its dose to overcome refractoriness and improve treatment outcomes.

Background. Methotrexate (MTX) in high doses (1–5 g/m²) is a key component of treatment protocols for acute lymphoblastic leukemia (ALL) in children. Interindividual variability in MTX toxicity is a crucial area of research aimed at enhancing the safety of therapy while maintaining its effectiveness.

Objective. To evaluate the role of polymorphisms of genes ABCB1 (C3435T, C1236T, 2677G>T/A, rs4148738c>T), SLCO1B1 T521C on the safety profile of methotrexate in children with ALL.

Materials and methods. The study is involved 124 patients with a confirmed diagnosis of ALL (C91.0 according to ICD-10) who underwent high-dose methotrexate treatment (greater than 1 g/m2). The severity of adverse reactions (ARs) was assessed using laboratory methods based on the National Cancer Institute's toxicity criteria (CTCAE v5.0 2018). The carriage of polymorphic variants was determined using allele-specific polymerase chain reaction (PCR) in real time. The results were statistically analyzed using the SPSS Statistics 26.0 software (USA).

Results. The safety analysis of high-dose MTX therapy revealed that the ABCB1 1236C>T polymorphism is a significant predictor of oropharyngeal mucositis during MTX treatment, with a higher risk for CC homozygotes. Patients with the TT genotype of the SLCO1B1 T521C rs4149056 gene have a 2.7-fold increased risk of severe infectious complications, while patients with the TT genotype of the ABCB1 C3435T gene have an elevated risk of nephrotoxicity (p = 0.035, OR: 8.3 (95 % CI: 0.83–82.2) and neurotoxicity (p = 0.041, OR: 2.3 (95 % CI: 1.02–5.12).

Conclusion. The results of the safety analysis of high-dose MTX therapy indicate the need for comprehensive pharmacogenetic testing before implementing this treatment in clinical practice.

Background. Treatment of patients with tuberculosis (TB) with multidrug-resistant (MDR) causative agent is often complicated by adverse reactions (AR) with forced drug discontinuation, its effectiveness is far from the target indicators and depends on a number of factors, including the patient's genetic characteristics. Pharmacogenetic markers of MDR-TB have not been studied; it is expected that their identification will improve the results of treatment based on a personalized approach.

Objective. to determine the pharmacogenetic markers associated with the efficacy and safety of treatment of patients with MDR TB.

Methods. A prospective cohort study included 40 patients with MDR-TB without HIV infection who received therapy with bedaquiline, linezolid, and a fluoroquinolone in 2023–2024. All patients had 3–5 ml of venous blood collected once, regardless of the duration of therapy. Real-time PCR was used to determine the presence of single-nucleotide polymorphisms in the genes for cytochromes (CYP3A4, CYP3A5), P-glycoprotein (ABCB1), the membranebound ATP-binding cassette transporter (ABCG2), and the organic anion transporter (SLCO1B1), which were selected based on literature analysis and the PharmGKB database. The relationship between these indicators and the effectiveness and safety of treatment was assessed using univariate analysis, with the calculation of the odds ratio (OR) and its 95 % confidence interval (CI).

Results. Target polymorphisms were identified: SLCO1B1 (rs4149056 — in 25.8 %), ABCB1 (rs1045642 — in 75.0 %, rs2032582 — 72.2 %, rs1128503 — 77.8 %), ABCG2 (rs2231142 — in 24.3 %), CYP3A4 (rs2740574 — in 8.1 %), CYP3A5 (rs776746 — in 10.8 %). The treatment efficacy based on the criterion of cessation of bacteriosis was 89.3 % (95 % CI 72.0–97.1 %); the incidence of adverse events was 70 % (95 % CI 54.5–82.0 %), with neurotoxic reactions prevailing (in 11 of 40 patients, 27.5 %). The AA genotypes of the CYP3A5 rs776746 gene and the AA genotypes of the ABCG2 rs2231142 gene were associated with a minimum frequency of cessation of bacterial shedding: respectively, in 33 % and 0% of individuals with each variant, compared to 100% in the rest, p < 0.01; OR 0.021 (95 % CI 0.001–0.77) and 0.083 (95% CI 0.01–0.98). The risk of neurotoxic reactions was higher in the presence of the "wild" variant (genotype GG) of the ABCB1 rs2032582 gene (55.6 % vs. 16.0 % in patients with allelic polymorphisms, p = 0.034; OR 6.3; 95 % CI 1.2–33.3); gastrointestinal reactions — in the presence of the TT genotype of the ABCB1 rs1128503 gene (50.0 % vs. 10.0 %, p = 0.045; OR=9.0; 95 % CI 1.22–66.2 %).

Conclusion. Polymorphisms of CYP3A5 (rs776746, AA genotype) and ABCG2 (rs2231142, AA genotype) genes were revealed, associated with unfavorable results of treatment of patients with MDR-TB. Genetic predictors of neurotoxic and gastrointestinal reactions during treatment of patients with MDR of the pathogen were determined.

Background. Approximately 30 % of rheumatoid arthritis (RA) patients exhibit inadequate response to methotrexate (MTX), with associated adverse effects limiting treatment efficacy, necessitating tools for predicting therapeutic outcomes [1]. The absence of robust pharmacogenetic models hinders personalized RA management.

Objective. This study aimed to develop a pharmacogenetic model to predict the risk of non-response to MTX in RA patients based on polymorphisms in genes encoding key proteins involved in MTX metabolism.

Methods. A prospective cohort study enrolled 281 RA patients meeting the European Alliance of Associations for Rheumatology criteria, receiving MTX as the initial disease-modifying antirheumatic drug. After 6 months, therapeutic response was assessed using the Disease Activity Score-28 (DAS28), identifying 170 responders and 111 non-responders. Genotyping was performed for polymorphisms in SLC19A1 (rs1051266), ABCB1 (rs1128503, rs2032582), GGH (rs3758149), FPGS (rs4451422, rs1544105), MTHFR (rs1801131, rs1801133), ATIC (rs2372536), ADA (rs244076), AMPD1 (rs17602729), ITPA (rs1127354).

Predictive models were developed using multifactor dimensionality reduction (MDR) and information analysis (Shannon entropy).

Results. The final model, incorporating five single nucleotide polymorphisms “ATIC rs2372536 + MTHFR rs1801133 + ADA rs244076 + MTHFR rs1801131 + SLC19A1 rs1051266”, achieved a sensitivity of 80.2 %, specificity of 69.4 % (OR 9.18 [95 % CI 5.19; 16.22]), and high cross-validation consistency (10/10).

Conclusion. This five-gene model demonstrates robust diagnostic performance for predicting MTX non-response in RA, with practical implementation via an “if-then” decision rule.

Relevance. The study of pharmacokinetic and pharmacodynamic drug interactions involving components of targeted medications demonstrates the lack of available data and the significant need for research aimed at describing the likelihood, extent, and clinical impact of proposed drug interactions for individual patients and for the population of patients with cystic fibrosis.

Objective. To describe a clinical case of a patient with cystic fibrosis F508del in the CFTR gene in combination with PIDS (Common Variable Immune Deficiency) a carrier of the potentially "problematic" CYP3A5 *3/*3 and SLCO1B1 *1/*5 genotypes for liver metabolism, with an assessment of the safety of the targeted therapy for cystic fibrosis.

Materials and methods. For genetic analysis, the isolated DNA was examined using the iPLEX Pro PGx panel (Agena Bioscience) in the "VeriDose® Core Panel" modification, the patient revealed: P-glycoprotein (P-gp) gene ABCB1 (rs1045642) G/G, APOE E2/E3, CYP1A2*1A/*1F, CYP2B6*1/*1, CYP2C19*1/*1 , CYP3A4*1/*1 , CYP3A5*3/*3 , PNPLA5 (RS5764010) C/C and SLCO1B1*1/*5 .

Results. The patient's biochemical abnormalities were clarified during the selection of a drug for targeted therapy of cystic fibrosis, as well as during the use and switching of targets. Clinically insignificant abnormalities in biochemical liver function parameters were not accompanied by clinical symptoms.

Conclusion. Modern pharmacogenetic testing capabilities have made it possible to identify a potentially "problematic" combination of CYP3A *3/*3 and SLCO1B1 *1/*5 genotypes in a patient, which is associated with changes in drug metabolism in the liver. Therefore, the use of pharmacogenetic testing in patients with genetic diseases opens up opportunities for personalization and improvement of pharmacotherapy safety, allowing for the prevention or delay of organ dysfunction to enhance.

A clinical case of a 35-year-old man with dissection of the left vertebral artery is presented, in connection with which dual antiplatelet therapy in the form of aspirin and clopidogrel, as well as anticoagulant therapy with enoxaparin, was prescribed to prevent the development of thromboembolic complications.

On day 5, the patient developed numbness in the right extremities, dysphagia and dysarthria, increased ataxia, left-sided ptosis, right-sided hemiparesis and hemihypesthesia. A control MRI scan of the brain revealed a focus of ischemia in the medulla oblongata. Pharmacogenetic testing was performed with the study of genetic resistance to antiplatelet drugs with the determination of polymorphic variants rs4244285*2, rs4986893*3, rs12248560*17 of the CYP2C19 gene. It was revealed that the patient was a carrier of the CT genotype according to the rs12248560 polymorphic variant, the GA genotype according to the rs4244285 polymorphic variant, and the GG genotype according to the rs4986893 polymorphic variant of the CYP2C19 gene. This corresponds to a variant of an intermediate metabolizer with an indistinctly defined effect of clopidogrel. The above clinical observation with the development of delayed ischemic stroke after spinal artery dissection (DPA) draws attention to the problem of genetic resistance to antiplatelet agents in this patient population. The development of delayed ischemic stroke in DPA is the basis for determining genetic resistance to antiplatelet agents and the subsequent possible change in treatment tactics.