Monogenic obesity: modern possibilities of targeted therapy

The prevalence of obesity in the Russian Federation continues to increase. Thus, among men, the prevalence increased from 10.8% in 1993 to 27.9% in 2017, among women – from 26.4% to 31.8%, respectively. Large-scale resources of genetic/genomic data, as well as objective reviews of genetic/genomic variants in cohorts of people with early development of obesity, especially in inbred populations, have led to the identification and characterization of rare and common genetic variants associated with the development of obesity. The increasing understanding of the prevalence of obesity caused by rare variants of the nucleotide sequence, as well as the identification of new genes associated with monogenic obesity, emphasize the importance of genetic analysis in assessing the cause of the disease. Most of the genes discussed in the review are involved in the leptin and melanocortin production system, however, genes regulating adipogenesis can also influence the development of obesity. Special attention should be paid to genetic testing of people with earlyonset severe obesity, especially in cases where it is accompanied by dysmorphic disorder, disorders of the nervous system or other systemic abnormalities. This testing can help in the accurate diagnosis and understanding of the causes of obesity, which, in turn, will allow the development of more individualized treatment strategies. The use of methods such as antisense oligonucleotides and gene editing technologies can significantly change treatment approaches, making them more effective.

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