RELEVANCE OF C677T AND A1298C POLYMORPHISMS OF THE MTHFR GENE, A66G OF THE MTR GENE, AND MTR A2756 WITH THE RISK OF CARDIOVASCULAR COMPLICATIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Summary. Currently, the prevalence of cardiovascular diseases, particularly arterial hypertension, is increasing among patients with rheumatoid arthritis (RA). In addition to traditional risk factors for cardiovascular complications (high blood pressure, hypercholesterolemia, overweight, diabetes, smoking, and unbalanced nutrition), there are additional factors, such as elevated homocysteine levels. This elevation results from disrupted folic acid metabolism. Identifying new factors is crucial for improving the diagnosis and personalized treatment of the combined course of rheumatoid arthritis and arterial hypertension. Objective. To analyze scientific research data on the role of folate metabolism disorders in patients with C677T and A1298C polymorphisms of the MTHFR gene, A2756G polymorphism of the MTR gene, A66G polymorphism of the MTRR gene, and rheumatoid arthritis in the development of cardiovascular diseases. Materials and Methods. Scientific and methodological literature from the databases PubMed, ELSEVIER, and Google Scholar for the years 2014–2023 was analyzed, selecting the most relevant information. The search was conducted using appropriate keywords: folate cycle, homocysteine, hyperhomocysteinemia, hypertension, rheumatoid arthritis. Results. This review presents current data on the functioning of the cascade mechanism of the folate cycle, the role of folate metabolism, and the connection of C677T and A1298C polymorphisms of the MTHFR gene, A2756G of the MTR gene, and A66G of the MTRR gene in the methylation process. The role of these polymorphisms as risk factors for the development of cardiovascular complications, including genes encoding methylenetetrahydrofolate reductase, methionine synthase, and methionine synthase reductase, was analyzed. The mechanisms of the influence of folate-dependent processes on blood pressure regulation in patients with rheumatoid arthritis and cardiovascular diseases are demonstrated. Contemporary options for their correction and the level of research on this topic are highlighted. The review also addresses key challenges and potential future research directions in this field. The article analyzes scientific studies aimed at investigating the role of folate metabolism disorders in patients with rheumatoid arthritis and examines their contribution to increased cardiovascular risk in patients with RA and hypertension associated with folate cycle polymorphisms. Conclusions. The C677T and A1298C polymorphisms of the MTHFR gene are associated with an increased overall cardiovascular risk in patients with rheumatoid arthritis. In contrast, research findings on the association of A2756G polymorphism of the MTR gene and A66G polymorphism of the MTRR gene, both involved in the folate cycle, with cardiovascular complications remain inconsistent.
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