RISK FACTORS FOR THROMBOEMBOLIC COMPLICATIONS IN PATIENTS WITH Ph-NEGATIVE MYELOPROLIFERATIVE DISEASES

Аннотация

In this paper, we studied theая prognostic significance rof the rs1801133 polymorphic locus of the MTHFR gene in the developmentof venous thromboembolic complications in patients with Ph-negativeMPD. The results obtained indicate that there is a tendency to form a hypercoagulable syndrome and the risk of thrombosis in patients with MPD with the presence of the unfavorable 677T allele of the MTHFR gene in the genotype. The results of the study indirectly indicate the regulatory "suppressive" effect of allelic variants 677T of the rs1801133 polymorphism of the MTHFR gene on the production of the MTHFR enzyme, leading to hyperhomocysteinemia, which is an important confirmation of the significance of genetic factors in the body's susceptibility to various thromboemboliccomplications in MPD. Key words: Ph-negative myeloproliferative diseases, methylenetetrahydrofolate reductase, hyperhomocysteinemia, thromboembolism. Relevance of the problem. Chronic Ph-negative миелопролиферативные myeloproliferativeоdiseases (MPD) are a group of pathogenetically identical hematological diseases, includingих erythremia, essential thrombocythemia (ET), and ideopathic myelofibrosis (IMF) [3, 6, 13]. These diseasesare caused by chronic leukemias with damage at the level of the hematopoiesis progenitor cell with unlimited proliferation of this cell characteristic of the tumor, the descendants of which are differentiated by all hematopoietic sprouts. (4, 7, 11). Classical chronic MPDs are acquired sporadic disorders of hematopoiesis, but hereditary forms of myeloproliferative diseases are also known-familial erythremia and thrombocythemia. Diagnosis and treatment of chronic MPD is an urgent problem of modern hematology. Until recently, the molecular defects and corresponding markers of IP, ET, and IMF were unknown. Therefore, the arsenal of routine laboratory methods used to diagnose classical Ph-negative chronic MPD was limited to the method of obtaining endogenous erythropoietin-independent colonies (EEC), evaluating clonality, and determining the level of erythropoietin and thrombopoietin in the blood of patients [1, 8, 12]. The recently increased interest in this disease is due to a significant increase in the frequency of diagnosis of chronic MPD in patients of different ages, as well as a high risk of developing thromboembolic complications in this category of patients, which are the main cause ofadverseoutcomes and mortality (2, 10). Methylenetetrahydrofolate reductase (MTHFR) isaurinary regulator of homocysteine metabolism in the blood. Carriage of an unfavorable genotypic variant of polymorphism C677T (rs1801133) of the MTHFR gene, which synthesizes a protein with reduced activity and increased thermal stability, is associated with the development of hyperhomocysteinemiain plasma, which is an independent risk factor for the development of various thromboembolic complications. Hypercoagulable condition in the form ofvenous thrombosis is one of the most serious complications in patients with Ph-negativeMPD. Despite intensive research, data on the role локуса C677of the C677t locus of the MTHFR gene in the formation of individual predisposition to certain thrombotic complications among patients with Ph-negative MPD remain very contradictory. This was the basis for conducting this study. Patients with MPH have a high risk of thrombotic complications, disease progression with transformation into secondary acute myeloid leukemia, and blast crisis [5, 9]. Due to the 63 INTERNATIONAL MULTIDISCIPLINARY JOURNAL FOR RESEARCH & DEVELOPMENT SJIF2019:5.2222020:5.5522021:5.6372022:5.4792023:6.5632024:7,805 eISSN:2394-6334 https://www.ijmrd.in/index.php/imjrd Volume12,issue05(2025) importance of molecular markers for both diagnosis and assessment of the risk of complications and the risk of disease progression, this study will allow us to assess the role C677of the C 677t polymorphism of the MTHFR gene in the development of thromboembolic complications in patients with Ph-negativemyeloproliferativediseases. Goals and objectives of the study. To assess the prognostic significance of polymorphic locus rs1801133 of the MTHFR gene with the development of venous thromboembolic complications in patients withPh-negative MPD. Materials and methods. The study included DNA samples from 69 patients with MPD (39- erythremia, 17-essential thrombocythemia, 13-subleukemic myelosis). Among these patients, 30 had various forms of thromboembolic complications. Genomic DNA extraction from peripheral blood cells was performed using the Ampli PrimeRIBOT Prep kit. Detection of the rs1801133 locus of the MTHFR gene was performed by allele-specific PCR on a thermocycler Applied Biosistems-2720 (USA), using kits of Litech LLC (Moscow), according to the manufacturer's instructions. Statistical processing of the results (case-control design) was performed using the OpenEpi statistical software package(ver.9.3). Theresults obtainedandtheir discussion. In the main and