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Журнал «Здоровье ребенка» Том 18, №3, 2023

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Генетично детермінована рецепція вітаміну D при метаболічно нездоровому ожирінні в дітей

Генетично детермінована рецепція вітаміну D при метаболічно нездоровому ожирінні в дітей

Авторы: A. Abaturov, A. Nikulina
Dnipro State Medical University, Dnipro, Ukraine

Рубрики: Педиатрия/Неонатология

Разделы: Клинические исследования

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Резюме

Актуальність. Геномні ефекти вітаміну D визначаються конформаційними змінами в структурі рецептора вітаміну D (vitamin D receptor — VDR), детермінованими однонуклеотидними варіантами (single nucleotide variants — SNV) гена VDR. Метою нашого дослідження є вивчення асоціації SNV гена VDR із метаболічно нездоровим ожирінням (МНО) в дітей. Матеріали та методи. Обстежено 252 дитини з ожирінням віком 6–18 років. Основну групу (n = 152) становили діти з МНО. Контрольну групу (n = 100) представили діти з метаболічно здоровим ожирінням. У 31 дитини основної та 21 дитини контрольної груп проведено повногеномне секвенування (CeGat, Germany). В усіх пацієнтів вимірювали рівень сироваткового 25-гідроксивітаміну D (Synevo, Ukraine). Для верифікації результатів застосовували розрахунок коефіцієнта кореляції Спірмена (r) і p-значення для кожної змінної, а також біоінформаційний аналіз. Результати. Ідентифіковано п’ять SNV гена VDR: rs2228570 (1 варіація числа копій ДНК (CNV): c.2T>C у 94,23 %); rs731236 (2 CNV: c.11056T>C, c.1206T>C у 65,38 %); rs10783218 (2 CNV: c.296+8C>T, c.146+8C>T у 7,69 %); rs2228572 (2 CNV: c.57C>T, c.207C>T в 1,92 %); rs12721365 (2 CNV: c.1059C>T, c.909C>T в 1,92 % пацієнтів). Кореляція між дефіцитом вітаміну D і SNV VDR відзначена для таких генотипів: AA rs12721365 (r = 0,41), AA rs2228572 (r = 0,39) та GG rs 2228570 (r = –0,27), p < 0,05. Кореляція між SNV VDR та МНО спостерігалася при таких генотипах: AA rs12721365 (r = 0,21), AA rs2228572 (r = 0,21), GG rs731236 (r = –0,15) та GG rs2228570 (r = –0,31), p < 0,05. ­Висновки. Генотипи AG SNV VDR rs12721365, rs2228572 високо асоційовані з розвитком МНО.

Background. Genomic effects of vitamin D are determined by conformational changes in the structure of the vitamin D receptor (VDR) determined by single nucleotide variants (SNV) of the VDR gene. The purpose is to study the association of the SNV of the VDR gene with metabolically unhealthy obesity (MUO) in children. 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 MUO. The control group (n = 100) consisted of children with metabolically healthy obesity. Whole genome sequencing (CeGat, Germany) was performed in 31 children of the main group and 21 controls. The level of serum 25-hydroxyvitamin D (Synevo, Ukraine) was measured in all patients. To verify the results, Spearman’s correlation coefficient (r) and p-value for each variable were calculated. Results. Five SNVs of the VDR gene were identified: rs2228570 (1 DNA copy number variation (CNV): c.2T>C in 94.23 %); rs731236 (2 CNV: c.11056T>C, c.1206T>C in 65.38 %); rs10783218 (2 CNV: c.296+8C>T, c.146+8C>T in 7.69 %); rs2228572 (2 CNV: c.57C>T, c.207C>T in 1.92 %); rs12721365 (2 CNV: c.1059C>T, c.909C>T in 1.92 % of patients). A correlation between SNV VDR and MUO was observed in the following genotypes: AA rs12721365 (r = 0.21), AA rs2228572 (r = 0.21), GG SNV rs731236 (r = –0.15) and GG rs2228570 (r = –0.31), p < 0.05. Conclusions. The genotypes AG SNV VDR rs12721365, rs2228572 are highly associated with the development of MUO.


Ключевые слова

ген рецептора вітаміну D; секвенування наступного покоління; аналіз однонуклеотидних варіантів гена; діти; метаболічно нездорове ожиріння

vitamin D receptor gene; next generation sequencing; analysis of single nucleotide gene variants; children; metabolically unhealthy obesity

doi: http://dx.doi.org/10.22141/2224-0551.18.3.2023.1581

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