Nataliia G. Gorovenko

Introduction. Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by demyelination and neurodegeneration. Emerging evidence suggests a potential role of folate metabolism, vitamin D status, and MTHFR gene polymorphisms in MS pathogenesis and progression. In populations without food fortification, such as Ukraine, these factors may be particularly relevant, highlighting the need to study their interrelationships with clinical disease features. Aim. To investigate the relationship between folate metabolism markers (homocysteine, folic acid, and vitamin B12), vitamin D levels, MTHFR gene variants, and the clinical characteristics of disease progression in patients with MS. Materials and methods. This study assessed biochemical markers of folate metabolism (homocysteine, folic acid, vitamin B₁₂), vitamin D levels, and the MTHFR rs1801133 genotype in 113 MS patients, with in-depth biochemical analysis conducted in a randomly selected subgroup of 36 patients. Clinical and demographic data were collected, and statistical analyses were performed to evaluate correlations between biochemical, genetic, and clinical parameters. Results. Patients demonstrated elevated median homocysteine levels and suboptimal concentrations of folic acid, vitamin B₁₂, and vitamin D. Significant inverse correlations were observed between homocysteine and folic acid levels, as well as between vitamin D levels and EDSS scores. Smokers had significantly lower vitamin B₁₂ levels. Although the difference was not statistically significant, patients with the TT genotype of MTHFR rs1801133 showed a trend toward lower folic acid levels. Homocysteine levels were highest in patients with secondary progressive MS, indicating a possible link to disease progression. Conclusions. Findings highlight the potential contribution of disrupted folate metabolism and vitamin D deficiency to MS pathogenesis, particularly in populations lacking food fortification. These results underscore the need for further research into vitamin-based interventions as possible strategies for modifying disease course.

Aim. Impairments in folate cycle function may play a role in the pathogenesis of multiple sclerosis (MS). Genetic variants of folate metabolism enzymes and transporters, particularly MTHFR (rs1801133, rs1801131) and RFC (rs1051266), may modulate the risk of MS development and its clinical course. Objective. To determine the impact of variants of the MTHFR (rs1801133, rs1801131) and RFC (rs1051266) genes, as well as their combinations, on the risk, progression, and potential prediction of neurological damage in MS, with a view toward identifying new preventive therapeutic strategies. Materials and Methods. The study included 113 MS patients and 70 healthy controls. Genotyping was performed using a polymerase chain reaction with restriction fragment length polymorphism analysis. Clinical evaluation included assessment of the Expanded Disability Status Scale (EDSS) score. Results. The 1298C allele of MTHFR (rs1801131) was associated with an increased risk of MS, while the 1298A allele had a protective effect. Additionally, the 80A allele and 80GA genotype of RFC (rs1051266) were linked to a higher risk of MS, whereas the 80G allele and 80GG genotype exhibited a protective effect. In patients with the 80GA genotype, the EDSS score was significantly lower compared to those with the 80GG and 80AA genotypes. A combined effect of variants of the MTHFR and RFC genes was identified, modifying the risk of MS and its clinical manifestations. Conclusions. Genetic variants of MTHFR (rs1801131) and RFC (rs1051266) impact the risk of developing and the course of MS. The combination of genotypes 1298AC+80GA was associated with an increased risk of MS, whereas 80GG, in combination with functionally favorable MTHFR variants, reduced this risk.

The is article is devoted to the manifestation of hepatomegaly syndrome in a rare metabolic disorder – type 1 Gaucher disease (GD). The objective: to evaluate clinical signs and potential diagnostic role of hepatomegaly syndrome in patients with type 1 GD in Ukraine. As well as to develop and propose the diagnostic algorithm for GD, taking into account the hepatomegaly syndrome as a key clinical sign. Materials and methods. A retrospective clinical study was conducted involving 82 patients with type 1 GD diagnosed in Ukraine over a 21-year period (2002–2023). The patients underwent complex clinical examination of the manifestations of the disease, which included a detailed medical history collection, physical examination, as well as instrumental and laboratory evaluation of liver and spleen. Ultrasound examination was used to assess the sizes and structure of liver, while functional markers were evaluated through serum transaminase and ferritin levels. Results. Clinical symptoms and diagnostic findings were analyzed in 82 patients with confirmed type 1 GD in Ukraine. Comprehensive examination revealed hepatomegaly in 47 patients (57.32%) at the time of diagnosis, often in combination with other clinical signs. According to the clinical observations in Ukraine, liver enlargement was not depended on the presence of splenomegaly or history of splenectomy. Isolated hepatomegaly as an initial disease manifestation is rare (7.3%), but in some cases it is the only symptom at the time of diagnosis. Subsequently, most of these patients progress to classical hepatosplenomegaly accompanied by hematological disorders. Ferritin level was found to correlate with the degree of hepatomegaly, showing statistically significant elevations in patients with liver enlargement exceeding 1.25 times (odds ratio (OR) 30.17; p = 0.002) and especially ad increase of more than 1.5 times (OR 89.28; p = 0.0041). Such elevated ferritin level was present in only 54–67% of patients with hepatomegaly, thus this marker cannot be considered a universal diagnostic indicator of liver damage in GD. Conclusions. Hepatomegaly is a common clinical manifestation of type I GD. It was identified in 91% of patients in Ukraine at the time of diagnosis confirmation. The severity of hepatomegaly did not depend on whether splenectomy had been performed. Isolated hepatomegaly was uncommon (7.3%) and, in some cases, it was the only clinical symptom. A significant correlation was found between ferritin level and the degree of hepatomegaly. Based on the findings, a diagnostic algorithm was proposed that may be useful for early disease identification.

Autism spectrum disorders (ASD) are characterized by clinical heterogeneity and may be associated with cerebral folate deficiency (CFD). Among the causes, folate receptor alpha autoantibodies (FRAA) and variants of the SLC19A1 gene are commonly highlighted. The aim of this study was to analyze the rs1051266 variant of the SLC19A1 gene in patients with ASD and CFD and to determine its relationship with clinical and laboratory parameters. The study included 227 children with ASD, 156 of whom had CFD. FRAA detection, genotyping of the rs1051266 variant, and folate metabolism marker measurement (homocysteine, vitamins B9, B12, B6) were performed. FRAA binding was detected in 39.2% of ASD patients, blocking FRAA in 3.5%, and a specific soluble folate receptor in 13.2%. The 80GA genotype was the most common (46.3%), and homocysteine levels tended to be moderately elevated (upper quartile – 7.0). Significant correlations were found between homocysteine levels and vitamins B9, B12, and B6 (p < 0.05) and between verbal impairments and vitamin B12 (p = 0.043). In ASD and CFD patients, the 80GG genotype was more frequent (p = 0.03) and vitamin B12 levels were elevated (p = 0.021). In the ASD group, correlations were found between the 80AA genotype and demyelination (p = 0.020) and between homocysteine levels and demyelination (p = 0.042). In conclusion, the rs1051266 variant of the SLC19A1 gene modifies the clinical course of ASD. Patients with ASD and CFD exhibited high variability in folate metabolism markers. These findings underline the need for further research on folate transport genetics for personalized prevention and treatment strategies for ASD and CFD.

Дослідження загальних властивостей і закономірностей розвитку живих організмів, вивчення видового різноманіття, а також хімічні процеси, що відбуваються всередині живих організмів, – ці знання, які надають науки біологія та біохімія, сприяють розв’язанню проблем людства: доступності достатньої кількості їжі, збереження здоров’я населення, збереження та покращення якості довкілля. Перебуваючи в постійному розвитку та вивчаючи ці важливі питання сучасні біологія та біохімія являють собою трансдисциплінарні галуззі знань, що потребують конкурентоспроможних, ініціативних, кваліфікованих, інтегрованих в європейський і світовий науково-освітній простір спеціалістів. Біологія та біохімія поряд із іншими природничими науками сприяють новим відкриттям, що істотно підсилюють рівень світової сучасної охорони здоров’я: від персональної медицини до біологічних основ психології людини, від розроблення нових біонічних матеріалів і пристроїв до клітинної інженерії. Життя розглядається на різних рівнях його організації – від молекули до біосфери, а узагальнення біохімії допомагають висвітлити еволюцію органічного світу та питання про виникнення життя на Землі.Отже, представлено новітнє бачення здобуття освіти майбутніх докторів філософії за спеціальністю 091 «Біологія та біохімія» галузі знань 09 «Біологія». Серед особливостей сучасної біології та біохімії виділяємо: комплексність та невизначеність умов, що передбачають застосування законів, теорій і методів природничих наук; вивчення взаємозв’язку біологічного та соціального розвитку людини; системну біомедицину; процедури і методи для вивчення діагностики та терапії захворювань і оцінювання здоров’я. Безумовно, ці особливості та всі напрями спеціальності, пов’язані із застосуванням інформаційних і цифрових технологій, штучного інтелекту.По завершенню навчання, здобувачі вищої освіти третього рівня мають оволодіти загальнонауковими компетентностями, здобути універсальні навики дослідника та мовні компетентності. Тематика курсу професійної підготовки розроблена з метою сприяння здатності інтегрувати знання та розв’язувати складні завдання в мультидисциплінарних і трансдисциплінарних контекстах.

Introduction. Currently, hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are among the most widely used hypolipidemic drugs worldwide. However, to date, the problems of the insufficient effectiveness of statin therapy and the development of unwanted side effects in patients remain not fully resolved. The identification of key variants in genes whose protein products are involved in statin metabolism and their effect on carriers during therapy may improve the efficacy of statin treatment and help prevent unwanted side effects, and therefore may be a valuable tool for clinicians when monitoring the progress of patients. to whom these medicines were prescribed. Aim. To summarize the information available in the literature on variants in genes that affect the effectiveness and safety of statins during treatment. Materials and methods. An assessment of the current literature on the role of genetic variants in the effectiveness and safety of statins was made. The search was performed in Scopus, Web of Science, Google Scholar, and PubMed databases. Results. The chemical structure and metabolism of statins are described. A review of the current literature on the impact of variants in ABCB1, ABCG2, CYP3A4, CYP3A5, and SLCO1B1 genes on the effectiveness of statin therapy and the development of unwanted side effects in patients is presented. These genes have been shown to be associated with the pharmacodynamics and pharmacokinetics of statins, which affect their efficacy and safe use. Conclusions. Since recent studies have demonstrated the influence of protein transporters such as ABCB1, ABCG2, OATP and BCRP, as well as the cytochrome P450 system, on the pharmacokinetics and pharmacodynamics of statins, further large-scale studies focusing on drug transporters are needed. The review focused on finding correlations between polymorphic variants in the genes encoding the aforementioned transporters and CYP enzymes and the efficacy and safety of statins. The presented data of the literature emphasize the importance of pharmacogenetic studies of statins, which can be useful to clinicians to minimize the negative consequences of taking these drugs and improve the effectiveness of treatment of patients who are carriers of risk alleles.

The neuronal ceroid lipofuscinosis type 2 (CLN2) is a heterogeneous group of neurodegenerative lysosomal storage disorders caused by autosomal recessive inheritance of two pathogenic variants in trans in the TPP1 gene. Classical late‐infantile CLN2 disease has a very well‐defined natural history. However, a small number of patients with TPP1 enzyme deficiency present a later onset or protracted disease course within this group there are phenotypic variants. Our work aimed to identify pathological variants in the TPP1 gene that conditioned the development of CLN2 disease in Ukrainian patients, to compare these variants with those found in patients from other European and non‐European regions, and to make genotype–phenotype associations for this disease. The phenotypes and genotypes of the 48 CLN2‐affected individuals belonging to 43 families were profiled through clinical data collection, enzyme analysis, and genotyping. In most patients, genotype and phenotype correlation are in keeping with the data of previous studies. The clinical signs of the disease in patients with new, previously undescribed variants, allowed us to augment existing data about genotype–phenotype correlations for CLN2 disease. The combination of genotype and clinical form of the disease demonstrated that predicting the type and clinical course of the disease based on genotype is very complicated. The data we obtained supplements existing information on genotype–phenotypic correlations in this rare disease, which, in turn, lays the foundation for a personalized approach to the management of this disease.

Background The pro-inflammatory cytokine IL-1 plays an important role in severe COVID-19. A change in IL-1 production may be associated with a mutation in the IL1Β gene. Our study analyzed the impact of the IL1Β gene variants (rs1143634) on disease progression in patients with severe COVID-19 pneumonia, taking into account treatment strategies. Methods and results The study enrolled 117 patients with severe COVID-19 pneumonia. The IL1Β gene variants were identified using the polymerase chain reaction-restriction fragment length polymorphism method. In the group of patients, the following genotype frequencies were found based on the investigated rs1143634 variant of the IL1Β gene: CC–65.8%, CT–28.2%, and TT–6.0%. Our results showed that the group of patients with the T allele of the IL1Β gene had higher leukocyte counts (p = 0.040) and more pronounced lymphopenia (p = 0.007). It was determined that patients carrying the T allele stayed on ventilators significantly longer (p = 0.049) and required longer treatment with corticosteroids (p = 0.045). Conclusion Identifying variants of the IL1Β gene can be used as a predictive tool for assessing the severity of COVID-19 pneumonia and tailoring personalized treatment strategies. Further research with a larger patient cohort is required to validate these findings.

Background: Previous studies indicate a close relationship between the severity of COVID-19 and oxidative stress. N-acetyltransferase 2 (NAT2) is an enzyme that metabolizes a wide range of xenobiotics and plays an important role in the regulation of reactive oxygen species, consequently contributing to the development of oxidative stress. Aim: To determine the impact of NAT2 gene variants on the risk of developing and the progression of severe COVID-19-associated pneumonia in patients from the Poltava region of Ukraine. Methods: The study included 117 patients who were diagnosed with severe COVID-19 pneumonia and received treatment in the intensive care unit. The NAT2 gene variants were identified through the PCR-RFLP method. Results: The presence of the AA genotype of the A803G variant in patients with severe COVID-19 pneumonia is associated with an almost 3-fold reduction in the risk of lethal outcomes. The presence of the TT genotype of the C481T variant was associated with the need for artificial lung ventilation. Patients in the study group with a heterozygous GA genotype of the G590A variant demonstrated a notable rise in the risk of developing systemic inflammatory response syndrome and acute respiratory distress syndrome, with a nearly 2.5-fold and 3-fold increase, respectively. The G857A variant was not associated with the risk of developing the above-- mentioned complications in the examined patients. Conclusion: The obtained results suggested that the NAT2 gene variants might influence the incidence, course, and adverse consequences of COVID-19.