Euphytica

Kalashnikova C.E., Shrayner E.V., Bystrova V.I., Lifshits G.I.

Recently, the role of metabolic syndrome (MS) has become crucial. There is a tendency for this disease to increase not only in the Russian Federation and throughout the world. According to World Health Organization data for 2022, approximately 60% of the European population is overweight or obese. The United States and Russia have the largest numbers of obese individuals. MS often occurs in developed countries, mainly in the adult population, and is a comorbid pathology. MS increases the risk of future disability and mortality. Despite the environmental factors that increase the risk of MS, genetic factors are also involved in the development of this pathology. The genes involved in the development of MS: MC4R, LEP, LEPR, PCSK1, ADCY3, POMC, and MRAP2, were identified. These genes and MRAP2 were identified and involved in the leptin-melanocortin signaling pathway, namely, they regulate energy metabolism, which, when a mutation occurs, leads to nonsyndromic monogenic obesity. MS is a multifactorial pathological condition that includes four independent sub-syndromes: obesity or overweight, hypertension, dyslipidemia, and insulin resistance. This article describes the features of genes contributing to the development of MS as well as the clinical features of the MS course.

Kirolos E.

Introduction. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has been recognized as a revolutionary advancement in the biomedical field, offering unparalleled precision and versatility in genome editing. This review examines the transformative potential of CRISPR as a diagnostic and therapeutic tool for various diseases.Methods. A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of PubMed, Scopus, Google Scholar, and Web of Science was performed to identify relevant Studies published between January 2015 and January 2025. The inclusion criteria focused on peer-reviewed articles discussing CRISPR-based diagnostics, therapeutic applications, and technological advancements. Studies were screened, assessed for quality using the CASP framework, and categorized into thematic areas for analysis.Results. CRISPR-based diagnostic platforms, such as SHERLOCK and DETECTR, were analyzed for their sensitivity and rapidity in detecting pathogens, cancer biomarkers, and genetic mutations. Emerging innovations, including prime and base editing, have been explored for their role in expanding the capabilities of CRISPR. Additionally, advancements in delivery mechanisms and the use of alternative Cas proteins have been discussed for their impact on clinical applicability.Conclusions. Ethical, regulatory, and accessibility challenges associated with CRISPR technology are highlighted, emphasizing the importance of responsible development and equitable deployment. This review connects cutting-edge advancements with translational challenges and underscores the significant role of CRISPR in shaping the future of precision medicine and global health.

Kantemirova B.I., Komarova O.V., Romanova A.N.

Interest in the rational prescription of medicines, considering the genetic characteristics of patients, is increasing every year. In foreign medicine, pharmacogenetic testing is often used as the main tool for selecting individual therapy. The most significant interest has been shown in candidate genes involved in changing the pharmacological response to therapy in patients with cardiovascular diseases because of the high risk of mortality. In most cases, cardiovascular disorders are accompanied by high blood pressure, which can be reduced using ACE inhibitors. However, data on the effectiveness and safety of drug use vary depending on the gender, race, or ethnicity of patients, making it more difficult to develop a unified algorithm for the introduction of pharmacogenetic tests into clinical practice. The authors of this review attempted to systematize the data obtained from various studies and identify the presence of clinically significant correlations between changes in the effectiveness of ACE inhibitors and the presence of polymorphism of candidate genes of the renin-angiotensin-aldosterone system.

Leonova M.V.

Cough is a common side effect of angiotensin-converting enzyme (ACE) inhibitors, requiring the discontinuation of these medications. The frequency of dry cough in patients treated with ace inhibitors was approximately 1.5–11%, according to a previous study of 35%. The exact mechanism underlying cough caused by ACE inhibitors remains unclear, with the bradykinin pathway being the most widely accepted theory. The roles of genetic polymorphisms in enzyme proteins and ACE inhibitors have been actively discussed by the medical community. Thus, the first studies to assess the role of genetic factors focused on the polymorphism of the ACE (I/D) gene and different loci of the bradykinin B2 (BDKRB2) receptor gene. Subsequently, several meta-analyses of studies confirmed the relationship between the polymorphism of the ACE I/D gene (rs4646994) and the bradykinin B2 58T/C receptor gene (rs1799722). Other genes at potential risk of developing ACE inhibitors may encode transporter proteins that affect plasma ACE inhibitors or membrane transport proteins such as ABO and SCLO1B1 (OATP1B1), whose polymorphism is associated with cough. Genome-wide association studies (GWAS) searched for new candidate genes responsible for the development of cough caused by ACE inhibitors, and links were found with gene polymorphisms CLASP1, KCNIP4, PREP, NTSR1, L3MBTL4, SRBT1, PNPT1, and PCGF3, among which many genes are responsible for the neurobiological mechanisms of cough development. The results of pharmacogenomics studies have expanded the understanding of the pathophysiological processes underlying ACE-associated cough. According to the results of the GWAS studies, a polygenic prognosis of the risk of developing cough and discontinuation of ace inhibitors is possible, which in the future may identify patients at risk of developing ace-associated cough.

Tyulkova T.E., Tkachuk A.P., Akmalova K.A., Abdullayev S.P., Mirzaev K.B., Sychev D.A., Manuylov V.A.

The introduction of genetics into medicine has unlocked the ability to predict drug efficacy and/or toxicity, and pharmacogenomics makes an important contribution to personalized medicine and pharmacotherapy. Pharmacogenetic testing identifies genetic variants that alter the response to a drug. At the same time, up to 95 % of the population is a carrier of at least one genetic variant; however, a patient may be a carrier of several genetic variants at the same time, which may be important not only in cases of prescription of a particular drug but also of other drugs during the future life. In this regard, two pharmacogenetic approaches are relevant — reactive or preventive testing. The current trend is pharmacogenetic panel testing as a model for precision medicine. In a multiplex panel model, several gene variants affecting drug response are tested simultaneously, and the data are stored for future use.However, practicing physicians have difficulty with genetic information because of low awareness of pharmacogenomics or lack of proper infrastructure and IT tools. Despite the publication of pharmacogenomics guidelines in the US (CPIC) and in the European Union (DPWG), most patients are still treated according to standard clinical practice. It was strategically important to establish interdisciplinary working groups — pharmacogenomics consortia — in the USA and the European Union, the purpose of which is to introduce pharmacogenetics into widespread clinical practice. The activities of these consortia and the results achieved are presented. In the work of consortia, various studies are used to analyze the level of knowledge on pharmacogenomics, applicationof pharmacogenetic testing, and clinical results, including different methodological approaches. The foreign experience (USA, European Union, China) in the dissemination and implementation of pharmacogenomics in real clinical practice is presented.

Vavilin V.A., Goreva O.B., Shebunyaeva Y.Y., Makarova S.I., Voitko M.S., Grishanova A.Y., Pospelova T.I.

Leonova M.V.

Nasyrova R.F., Kidyaeva A.V., Grechkina V.V., Shnayder N.A.

Devald I.V., Khodus E.A., Myslivtsova K.Y., Khromova E.B., Ignatova G.L., Lila A.M., Stashkevich D.S.

Baturin V.A., Ivanova A.V., Tsarukyan A.A., Muravyov K.A.

Miroshnikova V.V., Pchelina S.N., Donnikov M.Y., Vorobyev A.S., Tsay V.V., Kovalenko L.V., Glotov O.S.

Cardiovascular diseases (CVD) are a leading cause of mortality in many countries worldwide. Genetic testing is an integral part of CVD prevention. The most common hereditary diseases in the practice of a cardiologist are cardiomyopathy and channelopathy (arrhythmogenic syndromes), as well as familial hypercholesterolemia, which causes a high risk of atherosclerosis and coronary heart disease (CHD). The total carrier frequency of pathogenic variants is 1:100. Timely genetic diagnosis is necessary for conditions that can lead to sudden cardiac death (for example, long QT syndrome, Brugada syndrome, arrhythmogenic cardiomyopathies). Pharmacogenetic testing is also important in cardiology, since it allows taking into account the role of genetic factors in the formation of a response to therapy. Incorporating individual patient characteristics can increase efficiency and minimize the likelihood of complications. The design of modern targeted cardiopanels must necessarily take into account monogenic and oligogenic forms of dyslipidemia and cardiovascular pathologies, polymorphic markers associated with a violation of the lipid spectrum of blood plasma and the early development of CVD in a particular population, as well as a minimum set of pharmacogenetic markers according to modern recommendations for clinical pharmacologists. In this review we provide a justification for the optimal design of such a panel for use in medical practice and scientific research.

Kantemirova B.I., Abdullaev M.A., Chernysheva E.N., Kitiashvili I.Z., Zharkov Z.V., Romanova A.N., Konovalova E.R.

Coronary heart disease (CHD) is one of the most common causes of death worldwide. The pharmacokinetic properties of drugs used to treat coronary heart disease depend on genetic factors, including the genotype of CYP2C19, CYP2C9 and CYP4F2. However, existing studies of the genetic basis of the response to treatment in patients with acute coronary syndrome (ACS) have contradictory results, requiring a more detailed study. Goal. In this study, we studied the distribution of the genotypes of CYP2C19*2, CYP2C9*2 and CYP4F2*3 among 59 patients diagnosed with ACS who received dual antiplatelet therapy. Methods. The polymerase chain reaction (PCR) method was used to determine the genotypes of CYP2C19, CYP2C9 and CYP4F2. A correlation analysis of the results of genotype carriage and clinical and laboratory parameters of patients was carried out. Results. The distribution of CYP2C9*2 genotypes was as follows: wild genotype (CC) was found with a frequency of 78 % (45 patients), heterozygotes (CT) — 22 % (12 patients), homozygotes (TT) were not detected. The CYP4F2*3 genotype was distributed as follows: 56.14 % (32 patients) had a wild genotype (CC), 31.5 % (18 patients) were heterozygotes with reduced enzyme activity (CT), 12.36 % (7 patients) were homozygotes for the T (TT) allele. The distribution of alleles and genotypes of CYP2C9 did not correspond to the Hardy-Weinberg equation (χ2 = 21.55; p = 0.044), while the distribution of alleles and genotypes of CYP4F2 corresponded to it (χ2 = 3.61; p = 0.0574). Conclusion. The study showed a high prevalence of the genotypes CYP2C9*2 (CT) and CYP4F2*3 (CT and TT) among patients with acute coronary syndrome. The carriage of CYP2C19*2 was significantly associated with adverse cardiovascular events in patients. These results suggest that genetic testing can provide valuable information for risk stratification and personalized treatment of patients with acute coronary syndrome

Sirotkina O.V., Ulitina A.S., Zhilenkova Y.I., Zolotova E.A., Simakova M.A., Moiseeva O.M., Vavilova T.V.

Chronic thromboembolic disease (CTED) and chronic thromboembolic pulmonary hypertension (CTEPH) are the complications that comprise a serious problem for patients with history of pulmonary embolism (PE). Erythrocytes, extracellular microvesicles (EMVs) and miRNAs play a substantial role in the procoagulant states. The aim. To analyze the levels of miR-144-3р, miR-451a, and miR-451b in blood plasma-derived EMVs and erythrocytes in patients with history of PE and in the control group. Materials and Methods. 18 patients with history of PE (13 CTEPH, 5 CTED) and 8 controls were enrolled into the study. All the participants had undergone clinical and biochemical blood tests as well as the coagulogram. We used flow cytometry to assess plasma-derived EMVs (CD9, CD41, CD45, CD235a, CD105). We measured the expression of miR-144-3р, miR-451a, miR-451b by real-time PCR with endogenous control (miR-152-3p) and five exogenous quality controls. Results. The levels of miR-144-3р and miR-451a in patients were lower than in controls, both in EMVs (р = 0.030; р = 0.065) and in erythrocytes (р = 0.023;р = 0.086). In female patients, the levels of miR-144-3р and miR-451a in CTEPH were lower than in CTED (р = 0.087; р = 0.031). Mir-451b in EMVs has not been detected, while in erythrocytes its levels have not differed between the groups. In patients, the levels of miR-144-3р and miR-451a directly correlated with each other both in EMVs (р = 0.004) and in erythrocytes (р = 0.042). In all the participants, the levels of miR-144-3р and miR-451a in EMVs directly correlated with those in erythrocytes (р = 0.002; р = 0.078). The number of erythrocyte-derived EMVs correlated with miR-451a levels both in EMVs (R = 0.472; p = 0.065) and in erythrocytes (R = –0.829; p = 0.011). The level of miR-451a in EMVs correlated with blood plasma levels of factor VIII and fibrinogen (R = 0.584; p = 0.022 and R= –0.489; p = 0.047), and with the International Normalized Ratio (R = 0.894; p = 0.041). Conclusion. The microRNA-144/451 cluster may influence both the hemostasis system and the risk of post-thromboembolic complications development. In the present study, miR-144-3р and miR-451a showed themselves as protective factors in relation to both the development of PE and severity of post-thromboembolic complications.

Sychev D.A.

The Russian Congress «Pharmacotherapy Safety 360°: NOLI NOCERE!» was successfully held at the Russian Ministry of Health in May 2023, providing a high-level, expert platform to discuss current and topical issues of pharmacovigilance and pharmacotherapy safety for different patient groups, including pediatrics, gerontology and geriatrics, pregnant women, patients with orphan and oncological diseases. Extensive scientific topics covered the most significant aspects of the pharmacotherapy safety in various fields, including cardiology, gastroenterology, pulmonology and allergology, endocrinology, neurology, oncology and psychiatry. Over 280 speakers, moderators and lecturers, Russian and foreign experts including world-renowned scientists participated in the discussion of the key tasks facing modern science. The Congress covered issues promising for the further development of biopharmaceuticals, related to the application of artificial intelligence and neural networks.

Serebryakova A.V., Aliyev K.A., Sorokina L.E., Gritskevich O.Y., Zyablitskaya E.Y.

The interest in the problem of hereditary forms of breast cancer is due not only to the increase in the number of patients, but also to the existing features in relation to the phenotypic characteristics of these tumors, course features, and sensitivity to various therapy options. Unfortunately, the data of clinical trials that exist to date do not provide a complete picture of the course of various forms of hereditary breast cancer, sensitivity to therapeutic agents, adequate examination volumes and preventive measures. In this regard, there is a need to conduct prospective randomized trials to optimize treatment, screening and prevention programs. The rapid development of technologies in the field of molecular biology has made it possible to identify about 20 genes, the presence of mutations in which causes an increased risk of developing breast cancer. The aim of this review was to summarize the available data on the role of structural rearrangements of genes of varying degrees of penetrance associated with hereditary predisposition to breast cancer. The mechanism of hereditary breast cancer forms development is associated with rearrangements in DNA repair genes of varying degrees of penetrance. The identification of these mutations is of strategic importance for early diagnosis and the transition from an empirical to a targeted personalized approach in the treatment of various types of cancer. Understanding the pathogenesis of the disease at the molecular level makes it possible to make a breakthrough in the field of pharmacological innovations in order to create new selective classes of drugs in effective targeted therapy.