THE ROLE OF DNA METHYLATION DISORDERS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS
Keywords:
autoimmune thyroiditis, polymorphism, methylation, hypomethylation, homocysteine, hyperhomocysteinemia, hypothyroidism, euthyroidismAbstract
Autoimmune thyroiditis (AIT) is one of the most common autoimmune diseases of the thyroid gland and develops as a result of a complex interplay between genetic, environmental, and epigenetic factors. In recent years, particular attention has been paid to disturbances in DNA methylation, which are closely linked to folate metabolism and homocysteine turnover, with methylenetetrahydrofolate reductase (MTHFR) being a key enzyme in this pathway. The aim of this review was to analyze the role of MTHFR gene polymorphisms and the associated epigenetic and metabolic alterations in the pathogenesis of AIT. The review is based on data from systematic reviews, meta-analyses, and original clinical and laboratory studies published in leading international databases. It has been established that AIT is characterized by global DNA hypomethylation and differential methylation changes in key immunoregulatory genes, including NOTCH1, HLA-DRB1, TNF, and ICAM1. The MTHFR C677T and A1298C polymorphisms are associated with altered enzyme activity, elevated homocysteine levels, and an increased risk of hypothyroidism. Hyperhomocysteinemia, folate and B-vitamin deficiencies, as well as elevated thyroid-stimulating hormone (TSH) levels and positive anti–thyroid peroxidase antibodies (TPOAb) in euthyroid patients are shown to be interrelated components of early metabolic and epigenetic alterations in AIT. These findings support a potential role of methylation disturbances in the pathogenesis of AIT; however, further prospective studies are required to establish causal relationships.
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