Журнал «Здоровье ребенка» Том 18, №4, 2023

Актуальність. Однонуклеотидні варіанти (single nucleotide variant — SNV) гена греліну (GHRL) супроводжуються продукцією дефектного протеїну препрогреліну, що може призводити до розвитку ожиріння та метаболічних порушень. Мета: вивчити асоціації гена SNV GHRL із розвитком різних фенотипів ожиріння в дітей. Матеріали та методи. Обстежено 252 пацієнтів з ожирінням віком 6–18 років. Основну групу (n = 152) становили діти з метаболічно нездоровим ожирінням (МНО). Контрольну групу (n = 100) представили діти з метаболічно здоровим ожирінням (MЗO). У 31 дитини основної та 21 дитини контрольної групи проведено повногеномне секвенування (CeGat, Німеччина). Рівень інтерлейкіну (IL) 1β у сироватці крові визначали методом імунохемілюмінесцентного аналізу, IL-6 — методом імуноферментного аналізу (Synevo, Україна). Результати. Асоціація з розвитком MНO була вищою для T-алеля SNV rs696217 гена GHRL у здорових осіб (t = 2,31; p < 0.05) та пацієнтів з ожирінням (t = 2,06; p < 0,05). Генотип GT SNV rs696217 був пов’язаний з інсулінорезистентністю (r = 0,40; p < 0,05) у групі MНO і зворотно корелював з умістом холестерину (r = –0,45) та холестерину ліпопротеїнів низької щільності (r = –0,39). Генотип TA SNV rs4684677 корелював із рівнем IL-6 (r = 0,74) у групі MЗO та з IL-1β (r = 0,35) у групі MНO, p < 0,05. Профілактика трансформації MЗO в MНO визначається T-алелем SNV rs34911341 (t = 2,29, p < 0,05). Висновки. Міссенс-варіанти rs696217, rs4684677 гена GHRL є SNV, високо асоційованими з ожирінням та розвитком метаболічних порушень.

Background. Single nucleotide variants (SNVs) of the ghrelin (GHRL) gene are accompanied by the production of a defective preproghrelin protein, which can lead to the development of obesity and metabolic disorders. The purpose was to study the associations of SNVs of the GHRL gene in children with the development of various obesity phenotypes. Materials and methods. Two hundred and fifty-two obese children aged 6–18 years were examined. The main group (n = 152) was represented by patients with metabolically unhealthy obesity (MUO). The control group (n = 100) included children with metabolically healthy obesity (MHO). Whole genome sequencing (CeGat, Germany) was performed in 31 children of the main group and 21 controls. Serum levels of interleukin-1β were measured using a chemiluminescent immunoassay, interleukin-6 — by enzyme-linked immunosorbent assay (Synevo, Ukraine). Results. The association with the development of MUO was higher for the T allele of SNV rs696217 in healthy individuals (t = 2.31; p < 0.05) and obese patients (t = 2.06; p < 0.05). The GT genotype SNV rs696217 was associated with insulin resistance (r = 0.40; p < 0.05) in the MUO group and inversely correlated with levels of cholesterol (r = –0.45) and low-density lipoprotein cholesterol (r = –0.39) in children with MHO. The TA SNV rs4684677 genotype correlated with IL-6 levels (r = 0.74) in the MHO group and with IL-1β (r = 0.35) in children with MUO, p < 0.05. Prevention of the transformation of MHO into MUO is determined by the T allele SNV rs34911341 (t = 2.29, p < 0.05). Conclusions. The missense variants rs696217 and rs4684677 of the GHRL gene are SNVs highly associated with obesity and the development of metabolic disorders.

грелін; аналіз однонуклеотидних варіантів генів; діти; метаболічно нездорове ожиріння; метаболічно здорове ожиріння

ghrelin; analysis of single nucleotide gene variants; children; metabolically unhealthy obesity; metabolically healthy obesity

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