Endocrine Abstracts

Introduction: Metabolic syndrome (MS) is a disease that develops in obesity in adult patients with the development of numerous metabolic and vascular disorders. In patients with MS, the risk of developing cardiovascular diseases is increased compared to the general population by 1.78 times as a whole and 2.25 times in women. Currently, the number of overweight children and the development of metabolic complications such as fatty liver, hypertension, and type 2 diabetes are increasing. The role of genetic factors in the development of obesity and metabolic syndrome is not excluded.

Aim: The aim was to study genetic markers and chromosomal regions directly or indirectly associated with the obesity phenotype.

Results: Fifty syndromic and 8 monogenic forms of obesity are identified. Complete inactivation of 5 genes - LEP, LEPR, POMC, PCSK1 and MC4R is accompanied by severe hyperphagia and early onset of marked obesity in humans. The share of such hereditary options accounts for no more than 5% of all cases of obesity. The world literature describes 14 cases of complete deficiency of LEP, LEPR - 13, POMC - 7, PCSK1–3 and MC4R - 20 people. The deficiency of BDNF and its high-affinity receptor NTRK2 (TrKb), as well as SIM1, is associated with severe hyperphagic obesity in mice, and the partial defect also causes them to be hyperphagy and obesity. Leptin deficiency (LEP) - has autosomal recessive inheritance. Leptin receptor deficiency (LEPR) - also has autosomal recessive inheritance, similar to the leptin deficiency clinic. However, with a LEPR defect, signs are less pronounced than with LEP, and hypothyroidism is rare. Mutation of the proopiomelanocortin (POMC) gene is an autosomal recessive disorder accompanied by a defect in the anorexigenic action of melanocortin. Mutation of prohormone convertase 1 (PCSK1) is inherited autosomal recessively. The enzyme convertase prohormone 1 (KP 1) cleaves prohormone. A mutation of the 4 R - melanocortin receptor gene (MC4R) is transmitted autosomally dominantly. Melanocortins, as conductors of leptin signals, act through binding to the MC4 receptors. Mutations in the MC4 P gene also cause obesity. >3 mutations in the LEP gene and a series of mutations in the LERP gene that cause severe obesity in homozygotes have been identified. Partial failure of BDNF, NTRK2, SIM1 is accompanied by severe obesity with hyperphagia.

Conclusion: Identification of a large number of genes associated with obesity and the development of MS indicates the polygenicity of these conditions, the relevance of genetic expertise for diagnosis and therapy.