THE ROLE OF HYPERHOMOCYSTEINEMIA IN THE DEVELOPMENT OF COGNITIVE IMPAIRMENT IN CHRONIC CEREBRAL ISCHEMIA

Аннотация

C-reaktiv oqsil (CRP) va gipergomosisteinemiya darajasining oshishi endotelial shikastlanish va ateroskleroz rivojlanishining mustaqil omillari sifatida qaraladi. Endoteliyada yuzaga keladigan sust yallig'lanish jarayoni odatda infektsiyalar bilan bog'liq emas. Gomosistein to'planishi arteriyalar devorlarini bo'shashtirishiga, endoteliyada mahalliy nuqsonlarning paydo bo'lishiga olib keladi. Ushbu guruhdagi gomosistein darajasi yuqori bo'lgan odamlarda Altsgeymer kasalligi va kognitiv buzilish xavfi ortadi. Kalit so’zlari: C-reaktiv oqsil, gipergomosisteinemiya, kognitiv buzilish, Gomosistein. Relevance Cerebral ischemia is a neurodegenerative process that causes persistent oxidative damage to brain tissue, suppression of the tissue antioxidant defense system, and significant impairment of memory functions [1]. Factors that aggravate the degree of development of oxidative stress include homocysteine and its autooxidation products, mainly homocysteine acid. The concentration of the total level of homocysteine in the bloodstream increases with the development of neurodegenerative processes, such as Alzheimer's disease and Parkinson's disease [2–4]. Currently, an elevated level of homocysteine is regarded as an independent risk factor for cardiovascular and neurodegenerative diseases . Recent studies have shown that homocysteine is a more informative indicator of the development of cardiovascular diseases than total cholesterol, and is an independent factor in the formation of both stenocclusive lesions of the main arteries [4], deep vein thrombosis [2] and microangiopathy [3], and subsequent cerebrovascular events, especially in patients with coronary artery disease, kidney disease, type 2 diabetes mellitus . In 9.6% of patients with venous thrombosis, of the known risk factors for thrombosis, only hyperhomocysteinemia is detected [17]. According to a number of authors, an increase in the level of homocysteine by only 20-30% can lead to irreversible consequences, including ischemic stroke. An increase in the level of blood homocysteine by 5 μmol/l from the upper limit of the norm leads to an increase in the risk of atherosclerotic vascular lesions by 60% in men and 80% in women [2]. It is also known that hyperhomocysteinemia accompanies a number of oncological diseases. https://scientific-jl.com 2 4 0 46-son_1-to’plam_Iyun -2025 ISSN:3030-3621 Ta'lim innovatsiyasi va integratsiyasi Hyperhomocysteinuria and hyperhomocysteinemia are associated with defects in the molecules of cystathionine beta synthase and methylenetetrahydrofolate reductase. The methylenetetrahydrofolate reductase gene (C677T) is the replacement of cytosine with thymidine at position 677, which leads to the replacement of alanine with valine in the apoprotein of this enzyme. This is the most studied variant of the MTHFR gene polymorphism, in which homocysteine in the blood increases. Defects M5, M10- MTHFR in adulthood are observed in 54% of cases among all thrombophilic disorders and lead to hyperhomocysteinemia of intermediate and medium levels (more than 15 μmol/l). However, according to some data, the association of this mutation in the development of cerebrovascular diseases was noted in 16% of cases . The methylenetetrahydrofolate reductase gene (A1298C) is a variant of the MTHFR gene polymorphism with the replacement of adenine by cytosine at position 1298, which is not accompanied by an increase in the level of homocysteine in the blood. However, the combination of heterozygosity for 677T and 1298C alleles is accompanied by an increase in plasma homocysteine levels, a decrease in folate levels, and a decrease in MTHFR enzyme activity. Differences in genotypes: The difference between TT and CC MTHFR genotypes results in an average homocysteine difference of 2 μmol/L, which in turn, according to studies, has a 20% difference in the risk of stroke. The independent difference between TT and SS genotypes for stroke is 26% . The TT genotype has a worse prognosis for the development of stroke (compared to CT and SS). The relative risk of stroke with T allele carriage increases by 17% (OR=1.17, 95% CI 1.09-1.26), with the TT genotype the risk of stroke increases by 37% (OR=1.37; 95% CI 1.15-1.64), together with other risk factors, the prognosis worsens to a greater extent (T allele: OR=1.18; 95% CI 1.09-1.29; TT genotype: OR 1.48; 95% CI 1.22-1.8) [10]. The MTP methionine synthase gene (A2756G) - a polymorphism variant with the replacement of arginine by glutamine leads to factor V resistance to activated protein C, and, as a result, to an increase in thrombin formation and fibrin clot resistance, this leads to an uncontrolled blood coagulation process, which increases the risk of acute renal failure and cardiovascular disease. A decrease in the level of pyridoxine, cyanocobalamin, and folic acid in food causes hyperhomocysteinemia not only in homozygous carriers, but also in people without mutations in the homocysteine metabolism genes (low-