The article presents the key decisions and priority directions for the development of the specialty "Clinical Pharmacology" adopted following the congress of Clinical Pharmacologists "ClinPharm-Expert 2026," held on May 21–22, 2026 in Moscow within the framework of the IV Russian Congress "Pharmacotherapy Safety 360°: Noli nocere!" The document summarizes the main provisions of the congress Resolution, which specifies the pathways for implementing the Healthcare Development Strategy of the Russian Federation until 2030. Special attention is given to strengthening the role of clinical pharmacologists as key ambassadors of personalized medicine technologies, including pharmacogenetic testing and therapeutic drug monitoring. The Resolution formulates 19 organizational and educational measures aimed at updating the regulatory framework, integrating clinical pharmacologist consultations into the clinical-statistical groups system, developing networking educational programs, establishing a National Research Center for Clinical Pharmacology, and enhancing the prestige of the specialty ahead of its 30th anniversary in 2027. The article also highlights the inclusion of the journal "Pharmacogenetics and Pharmacogenomics" in the Scopus database and the "White List" of scientific periodicals. The article is intended for clinical pharmacologists, healthcare administrators, physicians of related specialties, and professionals in personalized medicine.

Background. The therapeutic response to ACE inhibitors in hypertension is variable and depends on a combination of clinical, behavioral, and pharmacogenetic factors. Mathematical modeling allows us to assess their contribution to achieving the target values of blood pressure.

Objective. To determine the factors associated with the achievement and non-achievement of target blood pressure values in patients with arterial hypertension receiving ACE inhibitors in monotherapy.

Materials and methods. A single-center observational pharmacogenetic study was conducted in the period from February to May 2025. Comparison groups were formed to achieve the target blood pressure values: <140/90 mmHg and ≥140/90 mmHg. The pharmacogenetic profile of patients was assessed by the presence/absence of polymorphisms of the ACE I/D (rs1799752) and CES1 (c.1168-33C>A). The outcomes of therapy were considered to be the achievement of target values of BP, ΔSAD, and ΔDAD. The following parameters were selected as the studied confounders of the regression model: the number of polymorphic D alleles in the gene ACE; the number of polymorphic C alleles in the gene CES1, age, the amount of salt consumed per day, the number of cigarettes smoked per day.

Results. The study included 90 patients of whom: 39 reached the target blood pressure values (43.3%), and 59 did not (56.7%). An increase in the number of ACE D-alleles was associated with an increase in SBP after therapy by 23.5 mmHg (95% CI: 20.68-26.41, p <0.001), DBP by 4.67 mmHg (95% CI: 3.59-5.94, p <0.001). An increase in salt intake by 1 g/day was accompanied by an increase in SBP by 0.54 mmHg (p=0.024), DBP – by 0.20 mmHg (p=0.041). Mathematical models explained 75.7% of SAD variability and 43.9% of DBP. The AUC of the logistic model was 0.97.

Conclusion. The number of polymorphic D alleles is associated with a therapeutic response and can be considered as a preliminary marker of ACE inhibitor efficacy (p<0.001).

Background. In the context of predictive medicine, personalized assessment of ischemic stroke risk based on molecular genetic testing is becoming increasingly relevant. Polymorphisms in folate cycle genes (MTHFR, MTR, MTRR), leading to hyperhomocysteinemia, cause endothelial dysfunction and accelerate atherogenesis. The role of the renin-angiotensin system (RAS) is no less important: genetic variations in the AGT and NOS3 genes are associated with arterial hypertension and altered vascular tone, which creates a predisposition to cerebrovascular accidents.

Objective. To identify associations between polymorphisms of folate cycle and renin-angiotensin system genes and the development of acute ischemic stroke and transient ischemic attack (TIA).

Methods. The observational study included 492 patients who were treated in hospital at the Institution Clinical Hospital No. 1 of the Presidential Administration of the Russian Federation in the period 2022–2025 and who signed informed consent for molecular genetic testing. A comparative analysis of clinical, laboratory, instrumental, and molecular genetic data (polymorphisms of MTHFR, MTR, MTRR, AGT, NOS3, and AGTR1) was performed between the ischemic stroke group (n=426) and the TIA group (n=66). Statistical analysis was carried out using the Mann-Whitney U test and Pearson's chisquared test.

Results. Stroke patients were older (73 vs 66 years, p=0.005) and more frequently male (43.4 % vs 27.3 %, p=0.013). The stroke group had significantly higher triglyceride levels (p < 0.001) and potassium levels (p < 0.001), as well as a higher frequency of pathological MRT findings (p < 0.001). Genetic analysis revealed a significant predominance in the stroke group of homozygous CC genotypes for MTHFR C677T (p=0.001), AGT174 (p=0.004), AGT235 (p < 0.001), and NOS3 (p=0.028). In contrast, the TIA group more frequently carried TT genotypes for C677T AGT235, and NOS3, as well as the heterozygous CT genotype for AGT174.

Conclusion. Molecular genetic testing of polymorphisms in folate cycle and renin — angiotensin system genes represents a promising tool for risk stratification and differential diagnosis of ischemic stroke versus TIA, and may serve as a foundation for personalized pharmacotherapy in the nearest future.

Background. High variability in individual response to controlled ovarian stimulation remains one of the main challenges in assisted reproductive technologies, and the prognostic value of most studied genetic markers shows conflicting results.

Objective. To evaluate the association of gonadotropin and sex steroid receptor gene polymorphisms with clinical pregnancy rates in women with tuboperitoneal infertility undergoing in vitro fertilization programs.

Materials and methods. This prospective pilot study included 96 patients (25–35 years old) with tuboperitoneal infertility and normal ovarian reserve. Two groups were formed: Group 1 (n=48) — pregnancy on the first attempt; Group 2 (n=48) — patients with a history of three or more previous unsuccessful attempts. The patients received standardized therapy using a short protocol with gonadotropin-releasing hormone antagonists and recombinant FSH. Genotyping was performed using microarray analysis (Infinium Global Screening Array-24 v3.0, Illumina).

Results. For the rs3020394 polymorphism of the ESR1 gene, a protective association was established between the A/A genotype (p=0.025; OR=2.553; 95% CI 1.120-5.820) and a negative predictive value of the homozygous G/G genotype. An association was found between the heterozygous C/T genotype of the rs2234693 (PvuII) polymorphism in the ESR1 gene and an unfavorable IVF outcome (p=0.024; OR=0.593; 95% CI 0.170-0.890).

Conclusion. The identified associations demonstrate the need for the development and further implementation of pharmacogenetic testing in the comprehensive evaluation of patients with tuboperitoneal infertility as a tool for personalized medicine.

Background. The effectiveness of in vitro fertilization (IVF) programs remains limited, which necessitates the search for new prognostic markers. The CYP2A6 gene is expressed in estrogen-sensitive tissues, and its activity is regulated by sex steroids, but the contribution of its polymorphisms to IVF outcomes remains poorly understood.

Objective. To determine the association between polymorphic variants of the CYP2A6 gene and IVF outcomes in patients with tubal-peritoneal infertility.

Materials and methods. A prospective pilot study included 96 women (mean age 31.4 ± 3.7 years) with tuboperitoneal infertility. All participants received therapy according to a short protocol with gonadotropin-releasing hormone antagonists and recombinant follicle-stimulating hormone. Nine polymorphisms of the CYP2A6 gene were analyzed by genome-wide genotyping on the Illumina iScan platform. Statistical processing was performed using Student's test, χ ² test and Monte-

Carlo permutation method.

Results. The rs8192733 C/C genotype is associated with a favorable outcome (OR = 6.922; 95 % CI: 2.592–18.486; p <0.001), while the G/G genotype is associated with a risk of implantation failure (OR = 0.053; 95 % CI: 0.017–0.160; p <0.001). For rs57837628, the G/G genotype is associated with a 2.4-fold increase in the odds of pregnancy (OR = 2.369; 95 % CI: 0.946–5.936; p = 0.010), the A/G genotype is associated with an unfavorable outcome (OR = 0.231; 95 % CI: 0.096–0.559; p <0.001). Significance was confirmed by the permutation test (p-perm <0.05).

Conclusion. An association was established between the CYP2A6 polymorphisms rs8192733 and rs57837628 and the outcomes of IVF programs in tubal-peritoneal infertility. The obtained data demonstrate the potential for their use as additional criteria in personalized patient management protocols in ART cycles.

Objective. To systematically review and critically appraise current evidence on genetic markers associated with the efficacy of anti-VEGF therapy in neovascular age-related macular degeneration (nvAMD).

Methods. A literature analysis covering the period 2005–2025 was performed, including candidate gene studies, meta-analyses, and genome-wide association studies (GWAS). Genetic variants in CFH, ARMS2/HTRA1, VEGFA, KDR, IL8, and SIRT1 genes were examined.

Results. The most reproducible associations with anti-VEGF response were found for CFH rs1061170 (Y402H), ARMS2 rs10490924, IL8 rs4073 (-251A/T) и VEGFA rs699947 polymorphisms. According to meta-analyses, carriage of the CFH rs1061170 risk allele is associated with reduced functional response (pooled OR=1.34, 95 % CI 1.10–1.63). However, the effect size is modest, results differ between European and Asian populations, and large RCTs have not confirmed the clinical utility of single SNPs. None of the studied markers possess sufficient predictive value for standalone use in routine practice.

Conclusion. Genetic markers associated with anti-VEGF therapy efficacy in nvAMD show moderate and heterogeneous effects. The development of polygenic prognostic models combining multiple SNPs with clinical and imaging parameters is a promising direction.

Introduction. Cardiac surgery patients are at high pharmacological risk due to comorbidities, polypharmacy, and cardiopulmonary bypass.

Search methods. A literature search was conducted in PubMed/MEDLINE, Web of Science, Scopus, and eLibrary.ru (2015-2025) using keywords: “pharmacogenetics AND cardiac surgery”, “warfarin pharmacogenetics”, “clopidogrel CYP2C19”, “SLCO1B1 statin myopathy”, “drug-gene interactions”. In total, 42 sources were selected and analyzed. Inclusion criteria: original studies, meta-analyses, systematic reviews, and clinical guidelines in English or Russian. Exclusion criteria: single case reports, experimental studies, conference abstracts without full text.

Results. VKORC1 and CYP2C9 polymorphisms account for 50–60 % of warfarin dose variability; genotyping reduces bleeding risk and accelerates time to therapeutic INR. Loss-of-function CYP2C19 alleles impair clopidogrel activation, increasing ischemic event risk. The SLCO1B1 variant is associated with higher risk of statin-induced myopathy. In the Russian population, the frequency of clinically relevant alleles is comparable to European populations. Drug — gene and drugdrug-gene interaction concepts may potentiate adverse outcomes. Implementation of pharmacogenetic testing is limited by organizational, financial, and educational barriers.

Conclusion. For cardiac surgery patients, a multiparametric algorithm incorporating multilocus genotyping (CYP2C9, VKORC1, CYP2C19, SLCO1B1, ABCG2), clinical factor assessment, and drug interaction evaluation is the most promising strategy.

Introduction. Lurasidone is an atypical antipsychotic with high affinity for 5-HT₂A, 5-HT₇, and DRD2 receptors; however, its use is limited by interindividual pharmacokinetic variability and dose-dependent adverse effects. Multi-omics approaches offer opportunities for personalized dosing.

Objective. To systematically review evidence on genomic, transcriptomic, and epigenomic biomarkers associated with lurasidone efficacy and safety.

Methods. A literature search was conducted in PubMed, Scopus, and RSCI (2010–2026) using keywords: lurasidone, pharmacogenomics, CYP3A4, HTR1A, microRNA, therapeutic drug monitoring. Of 187 initially identified publications, 83 sources were selected after screening.

Results. The rs6295 polymorphism of the HTR1A gene is associated with lurasidone efficacy in European schizophrenia patients. CYP3A4 is the main metabolizing enzyme: CYP3A4*1G (rs2242480) significantly affects clearance (CL/F: C/C — 330 L/h, T/T — 441 L/h); CYP3A4*15 requires dose adjustment up to 240 mg/day in carriers. In hepatic impairment, dose reduction to 20–40 mg/day is recommended. Transcriptomic studies identified 1907 differentially expressed genes, including modulation of PER1 and BMAL1, as well as neurotransmitter imbalance. MicroRNAs (miR-181b, miR-21, miR-122) are promising biomarkers for response prediction and CYP activity monitoring. Lurasidone monotherapy efficacy in bipolar II depression does not exceed 41.3 %.

Conclusion. The most clinically relevant markers are CYP3A4 (rs2242480, CYP3A4*15) and HTR1A (rs6295) polymorphisms, as well as microRNAs. Prospective studies are required to validate multi-omics panels in clinical practice.

Background. The prevalence of clopidogrel resistance among patients with cardiovascular diseases (CVD) reaches 30–40 %, significantly increasing the risk of recurrent myocardial infarction (MI) and other thrombotic events. Genetic polymorphisms in CYP2C19 and ABCB1 account for up to 40 % of the variability in antiplatelet response; however, data on Turkic populations, including the Chuvash, remain fragmentary.

Objective. To determine the frequencies of CYP2C19 (*2, *3, *17) and ABCB1 C3435T polymorphisms, as well as their association with recurrent MI and clopidogrel resistance in patients of Chuvash ethnic origin with CVD, including acute coronary syndrome (ACS).

Materials and methods. This prospective cohort study included 216 Chuvash patients (mean age 66.5 years) with CVD, including ACS, receiving dual antiplatelet therapy with clopidogrel. Genotyping of CYP2C19 (*2, *3, *17) and ABCB1 (3435C>T) polymorphisms was performed using real-time PCR. In a subgroup of ACS patients (n=30), ADP-induced platelet aGGreGAtion was assessed turbidimetrically on day 7 of therapy.

Results. Among Chuvash patients, a high frequency of minor alleles was observed: ABCB1 C3435T — 60.6 %, CYP2C1917 (–806C>T) — 28.7 %, whereas the frequencies of CYP2C192 and CYP2C193 were low (9.05 % and 1.85 %, respectively). Heterozygous CT genotype of CYP2C19*17 was associated with a higher rate of recurrent MI both in the overall cohort (19.8 % vs. 8.5 % in CC carriers; p=0.049) and in the ACS subgroup (30.2 % vs. 12.9 %; p=0.037, p~CC–CT~ =0.044). Laboratory platelet aGGreGAtion assessment revealed that the highest proportion of antiplateletresistant patients was observed among heterozygotes carrying the *1/*17 genotype (rapid metabolizer phenotype), whereas no resistance cases were recorded among *17/*17 homozygotes (ultrarapid metabolizers). No statistically significant associations with recurrent MI were found for CYP2C192, CYP2C193, or ABCB1 polymorphisms.

Conclusion. In Chuvash patients with CVD, including ACS, heterozygous carriage of CYP2C1917 is associated with recurrent MI, which contradicts the expected enhancement of clopidogrel antiplatelet effect (rapid metabolizer phenotype). This may indicate possible phenoconversion due to the interplay of genetic factors (ABCB1 C3435T) and drug — drug interactions (concomitant omeprazole use).

Relevance. The safety of stroke pharmacotherapy against the background of polypharmacy is of paramount importance in modern clinical practice. Genetic polymorphisms of cytochrome P450 genes, including the CYP2C9 gene, significantly contribute to drug responses and drug-drug interactions. The alleles with reduced function are CYP2C9*2 (R144C, rs1799853) and CYP2C9*3 (I359L, rs1057910).

Objective. Analysis of the frequency distribution of alleles and genotypes of the CYP2C9 gene (rs1057910, rs1799853) in stroke patients, taking into account possible drug interactions in real clinical practice in Arkhangelsk.

Materials and methods. A cross-sectional study was conducted on a sample of patients diagnosed with stroke, hospitalized in the neurology department of the regional vascular center of the First City Clinical Hospital named after E. E. Volosevich of the Arkhangelsk Region. Patients were divided into two groups: those initially hospitalized and those readmitted. Polymorphic variants of the CYP2C9 gene were studied: rs1057910 (Ile359Leu), rs1799853 (Arg144Cys) by real-time polymerase chain reaction using a Bio-Rad CFX96 Touch amplifier.

Results. The study included 81 patients aged 43 to 95 years with a diagnosed stroke. Statistically significant differences were observed in the blood potassium level of 4.2 (3,865–4,615) in the group with primary hospitalization and 4,575 (4.31–4,845) in the group with repeated hospitalization (р=0,022). Carriers of low-functional variants of the CYP2C9 gene were identified in both groups: Ile359Leu (rs1057910), Arg144Cys (rs1799853). Statistically significant differences between the CYP2C9 gene allele variants and the frequency of repeated hospitalizations are not detected (p>0.05). The analysis of pharmacotherapy in the study sample of post-stroke patients revealed potential undesirable drug interactions between clopidogrel and acetylsalicylic acid as a risk factor for side effects.

Conclusion. The study conducted in real clinical practice demonstrates the importance of introducing pharmacogenetic testing in stroke patients from the perspective of identifying potential drug interactions.