The role of molecular genetic alterations in genes involved in folate and homocysteine metabolism in multifactorial diseases pathogenesis

Resumo

The molecular genetic modifications in multiple genes involved in folate and homocysteine metabolism play the pivotal role in the development of hyperhomocysteinemia. Hyperhomocysteinemia is observed in 5% of patients worldwide and accompanies various multifactorial diseases, including neurodegenerative, autoimmune and vascular disorders and tumors. It should be noted that increased homocysteine level itself may point to some imbalance in the organism and represent a diagnostic marker of the development of some pathology. The present review describes the role of molecular-genetic modifications in one carbon metabolism accompanying different multifactorial diseases, including congenital birth defects, vascular disorders, diabetes, and hormone-dependent cancers such as breast and ovarian cancer. Data of the association between the SNPs in functionally significant genes involved in the one carbon metabolism and pathologies mentioned above were demonstrated. In addition, we firstly represent the data of the involvement of epigenetic factors (hypermethylation and miRNA) in regulation of these genes in multifactorial diseases. The section devoted to the role of molecular-genetic impairments in the genes involved in homocysteine metabolism associated with breast and ovarian cancer includes worldwide findings and our own results.