medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2017-96-5-422-426medlit-818Research ArticleГИГИЕНА ОКРУЖАЮЩЕЙ СРЕДЫENVIRONMENTAL HYGIENEИСПОЛЬЗОВАНИЕ ПРЕПАРАТОВ ВАЛЬПРОЕВОЙ КИСЛОТЫ В КАЧЕСТВЕ РЕФЕРЕНТНОГО ВЕЩЕСТВА ДЛЯ ИЗУЧЕНИЯ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКОГО МЕХАНИЗМА «ОБЕЗОГЕННОСТИ» РАЗРУШИТЕЛЕЙ ЭНДОКРИННОЙ СИСТЕМЫVALPROIC ACID AS A REFERENCE SUBSTANCE FOR THE STUDY OF THE MOLECULAR-GENETIC MECHANISM OF OBESOGENITY OF ENDOCRINE DISRUPTERSАксёноваМарина ГеннадьевнаAksenovaM. G.sibr@yandex.ruСиницынаО. О.SinitsynaO. O.noemail@neicon.ruКирилловА. В.KirillovA. V.noemail@neicon.ruКозловаО. Б.KozlovaO. B.noemail@neicon.ruБурдС. Г.BurdS. G.noemail@neicon.ruФГБУ «НИИ экологии человека и гигиены окружающей среды им. А.Н. Сысина» Минздрава РоссииA.N.Sysin Research Institute of Human Ecology and Environmental HealthГБОУ ВПО РНИМУ им. Н.И. Пирогова Минздрава РоссииN.I. Pirogov Russian National Research Medical University201721102020965422426Copyright © Аксёнова М.Г., Синицына О.О., Кириллов А.В., Козлова О.Б., Бурд С.Г., 20202020Аксёнова М.Г., Синицына О.О., Кириллов А.В., Козлова О.Б., Бурд С.Г.Aksenova M.G., Sinitsyna O.O., Kirillov A.V., Kozlova O.B., Burd S.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rjhas.ru/jour/article/view/818

Перфтороктановая кислота (ПФОК) и ее производные являются общепризнанными обезогенами. Препараты вальпроевой кислоты (ПВК) являются структурно схожими с этими химическими веществами. Целью исследования явилось изучение молекулярно-генетического механизма набора веса у пациентов, принимающих ПВК с использованием кандидатных генов, участвующих в метаболизме среднецепочечных жирных кислот. В группе 238 пациентов измеряли уровни инсулина и вес до и после 12 мес приема ПВК. Генотипирование SNP rs1801282, C > G (Pro12Ala) гена PPARγ и rs1799883, G > A (Ala54Thr) гена FABP2 проводили методом ПЦР в реальном времени. Для женщин, набравших вес с генотипом «СС» гена PPARγ, уровень инсулина был значимо выше (26,3 ± 1,7 мкМЕ/мл) в сравнении с ненабравшими вес (14,9 ± 3,1 мкМЕ/мл). Для мужчин, набравших вес с генотипом «СС» гена PPARγ, уровень инсулина был также значимо выше (25,4 ± 1,8 мкМЕ/мл) в сравнении с не набравшими вес (13,3 ± 2,9 мкМЕ/мл). Для женщин, набравших вес с генотипом «AA» и «AG» гена FABP2 уровень инсулина был значимо выше (32,1 ± 1,7 мкМЕ/мл) в сравнении с ненабравшими вес (17,1 ± 3,2 мкМЕ/мл). Для мужчин корреляции уровня инсулина с набором веса и генотипами не выявлено. Таким образом, структурно схожие со среднецепочечными жирными кислотами обезогены, в частности ПФОК и ее аналоги, могут влиять на набор веса по механизму развития инсулинорезистентности.

Perfluorooctanoic acid (PFOA) and its derivatives are recognized as obesogens. Clinically used valproic acid (VPA) as a drug is structurally similar to PFOA. The objective of the investigation was to study the molecular-genetic mechanism of the weight gain by patients taking the VPA drugs and correlation with candidate genes involved in the metabolism of medium chain fatty acids. Weight and basal insulin level were evaluated in 238 patients both before and after 12 months of VPA treatment. Genotyping of SNPs rs1801282, C>G (Pro12Ala) gene PPARγ and rs1799883, G>A (Ala54Thr) gene FABP2 were performed with TaqMan Real-Time PCR Assay. Women who gained weight were genotyped «СС» for the rs1801282 PPARγ gene and appeared to have significantly higher insulin level (26.3±1.7 uU/ml) as compared to women with the same genotype and without weight gain (14.9±3.1 uU/ml). Similarly, men who gained weight and were genotyped «СС» for the rs1801282 PPARγ gene, showed significantly higher insulin level (25.4±1.8 uU/ml) as compared to men with the same genotype and without weight gain (13.,3±2.9 uU/ml). Women who gained weight and were genotyped «AA» or «AG» for the rs1799883 FABP2 gene had significantly higher insulin level (32.1±1.7 uU/ml) as compared to women with the same genotype and without weight gain (17.1±3.2 uU/ml). No correlation of insulin levels with weight gain and genotypes were identified for men. Obesogens, structurally similar to the medium chain fatty acids (in particular PFOA and analogues), can affect weight gain through the development of insulin resistance.

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The authors declare that there are no conflicts of interest present.