Genetic structure of early morbid obesity in children in the Russian Federation: a pilot study

OBSERVATION. In the modern world, where overweight and obesity are becoming more and more widespread, a particularly alarming factor is the appearance of morbid forms among young children (up to 7 years old), which is the most atypical phenomenon and is of particular interest in the search for the causes of this pathology. According to the published data, about 7% of cases of severe pediatric obesity are associated with various genetic disorders. At the same time, the prevalence of monogenic and syndromal obesity in the Russian population remains unknown.

OBJECTIVE. To study the clinical features and genetic characteristics of patients with obesity occurring in early childhood.

MATERIALS AND METHODS. We examined 115 patients (49 girls (42.6% of cases, 95% CI [33.4; 52.1]), 66 boys (57.4% of cases, 95% CI [47.8; 66.5]) with obesity (SDS BMI >3.0) and the disease debut at an early age (up to 7 years). All patients underwent a comprehensive examination. Genetic study included full-exome sequencing by NGS (next-generation sequencing) or genetic analysis by methyl-sensitive multiplex ligase-dependent probe amplification (MS-MLPA) (in case anamnestic, phenotypic, clinical data suggestive of genomic imprinting diseases are identified).

RESULTS. In our study, 48.7% of children showed nucleotide sequence changes in the following genes: SNRPN, GNAS, MC4R, POMC, ALMS1, MKKS, BBS10, SIM1, PCSK1, LEP, ADCY3, MAGEL2, BBS1, BBS7, NTRK2, SH2B1, SEMA3A, LEPR, NRP2, MC3R, ADRB2, DYRK1B, KSR2, ENPP1, KCNJ11, FFAR4, PACS1, NAA10, METTL5, ADNP, TRIP12, SPEN, FAT1, KCNJ15, BAP1, TNPO2, MKLC1, SNRPN, GNAS. As per the results of the genetic study, the patients divided into 2 groups: group 1 — “genetic obesity”, group 2 — “obesity with unidentified cause”. The median age of patients at the time of examination was 8.2 years [5.5; 13.6], and the SDS of BMI was 4.0 [3.6; 4.4]. Patients in both groups were comparable in age, SDS of BMI, and SDS of height. In obese patients with an unspecified cause, an aggravated hereditary history of obesity was statistically significantly more common than in patients with genetic disorders (p<0.001). Polyphagia in patients with genetic disorders occurred in more than 79% of cases, whereas in patients with “simple” obesity this symptom was completely absent (p<0.001). The incidence of metabolic complications of obesity, such as carbohydrate metabolism disorders, insulin resistance, nonalcoholic fatty liver disease, and arterial hypertension did not differ statistically significantly between patients in both groups.

CONCLUSIONS. The high percentage of detected genetic alterations in our cohort might be explained by the strict criteria for inclusion of patients in the study, which emphasizes the relevance of this work. Further study of the pathogenetic mechanisms of obesity will contribute to the development of targeted therapy, which will allow the development of a personalized approach to the treatment and prevention of this disease.

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