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Abstract
Dysmetabolic conditions such as obesity, metabolic syndrome, and type 2 diabetes (T2DM) in the modern world have a steady trend of growth and have turned into a global medical and social problem. Both genetic predisposition and epigenetic modifications of gene expression, which regulate gene transcription at the epigenetic level, are involved in the pathogenesis of these conditions. The results of many studies indicate the relationship between folate cycle gene polymorphism and post-translational modifications of their products, as well as their significance in the occurrence and progression of T2DM and its cardiovascular, renal, and neurological complications. One of the most important epigenetic mechanisms of changing the expression of genes, whose products control key metabolic pathways, is DNA methylation. The methyl groups necessary for it are transferred within the folate cycle as part of methylated derivatives of folic acid. The process is catalyzed by DNA methyltransferases, of which methylenetetrahydrofolate reductase is a key enzyme, under conditions of reduced activity of which homocysteine will not be remethylated to methionine, which leads to an increase in its level in serum. In the condition of reduced action of this enzyme, homocysteine will not be remethylated to methionine, which leads to an increase in its level in serum. Since hyperhomocysteinemia is a known risk factor for vascular disease, methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, particularly the C677T mutation, may be responsible for endothelial dysfunction in T2DM in patients with the relevant genotype. DNA hypomethylation has been reported in liver biopsies from individuals with T2DM with low folate levels, whereas the MTHFR gene polymorphisms (T/T) polymorphism is associated with reduced enzyme activity. Clinical studies and a number of meta-analyses have established a relationship between MTHGFR gene polymorphism, levels of the homocysteine , and micro- and macrovascular disorders in diabetes mellitus, which indicates geneepigenetic mechanisms through which vascular complications of diabetes develop. Elevated levels of homocysteine and deficiency of folic acid and vitamin B12 can be a non-invasive clinical marker of DNA methylation disorders and the risk of vascular disorders in patients with T2DM.
References
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