phgenomicsФармакогенетика и фармакогеномикаPharmacogenetics and Pharmacogenomics2588-05272686-8849LLC "Izdatelstvo OKI"10.37489/2588-0527-2024-2-5-12USTDYYphgenomics-287Research ArticleАКТУАЛЬНЫЕ ОБЗОРЫCURRENT REVIEWГенетические факторы, способствующие развитию метаболического синдромаGenetic factors contributing to the development of metabolic syndromehttps://orcid.org/0009-0003-2324-7102КалашниковаК. Е.KalashnikovaC. E.

Калашникова Кристина Евгеньевна — врач педиатр, ординатор первого года Факультета медицины и психологии В. Зельмана

Новосибирск 

Christina E. Kalashnikova — pediatrician, first-year resident at the V. Zelman Faculty of Medicine and Psychology

Novosibirsk 

kristinafonina.1998@mail.ruhttps://orcid.org/0000-0003-3606-4068ШрайнерЕ. В.ShraynerE. V.

Шрайнер Евгения Владимировна — к. м. н., врач гастроэнтеролог, педиатр, доцент кафедры акушерства и гинекологии Факультета медицины и психологии В. Зельмана; н.с.

Новосибирск 

Evgenia V. Shrayner — PhD, Cand. Sci. (Med), gastroenterologist, pediatrician, Associate Professor of the Department of Obstetrics and Gynecology at the V. Zelman Faculty of Medicine and Psychology; researcher

Novosibirsk 

sch704@icloud.comhttps://orcid.org/0000-0003-3522-5384БыстроваВ. И.BystrovaV. I.

Быстрова Валерия Игоревна — студент Факультета медицины и психологии В. Зельмана

Новосибирск 

Valeria I. Bystrova — student at the V. Zelman Faculty of Medicine and Psychology

Novosibirsk 

https://orcid.org/0000-0001-9048-7710ЛифшицГ. И.LifshitsG. I.

Лифшиц Галина Израилевна — д. м. н., профессор кафедры внутренних болезней, Факультет медицины и психологии В. Зельмана; заведующая лабораторией персонализированной медицины

Новосибирск 

Galina I. Lifshits — Dr. Sci. (Med.), Professor of the Department of Internal Diseases at the V. Zelman Faculty of Medicine and Psychology; Head of the Laboratory of Personalized Medicine

Novosibirsk 

gl62@mail.ruНовосибирский государственный университетРоссияNovosibirsk State UniversityRussian FederationНовосибирский государственный университет ; Институт химической биологии и фундаментальной медицины СО РАНРоссияNovosibirsk State University ; Institute of Chemical Biology and Fundamental Medicine Siberian Branch of the Russian Academy of SciencesRussian Federation20243112202402512Copyright © Калашникова К.Е., Шрайнер Е.В., Быстрова В.И., Лифшиц Г.И., 20242024Калашникова К.Е., Шрайнер Е.В., Быстрова В.И., Лифшиц Г.И.Kalashnikova C.E., Shrayner E.V., Bystrova V.I., Lifshits G.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacogenetics-pharmacogenomics.ru/jour/article/view/287

В последнее время роль метаболического синдрома (МС) стала очень велика. Существует тенденция к увеличению данного заболевания не только в Российской Федерации, но и во всём мире. По данным ВОЗ 2022 г. сообщается, что около 60 % населения Европы имеет избыточную массу тела или ожирение. Известно, что США и Россия, представляют страны с наибольшим количеством жителей с ожирением. МС зачастую встречается преимущественно в развитых странах, в основном, у взрослого населения и является коморбидной патологией. Именно наличие МС увеличивает риск развития инвалидизации и смертности в будущем. Несмотря на факторы внешней среды, которые увеличивают риск развития МС, на сегодняшний день существует генетический компонент, также участвующий в развитии данной патологии. Среди генов выделяют те, которые участвуют в развитии МС: MC4R, LEP, LEPR, PCSK1, ADCY3, POMC, MRAP2. Эти гены принимают участие в лептин-меланокортиновом сигнальном пути, а именно регулируют энергетический обмен, что при возникновении мутации, приводит к несиндромальному моногенному ожирению. МС является многофакторным патологическим состоянием, которое включает в себя четыре самостоятельных подсиндрома: ожирение или избыточная масса тела, артериальная гипертензия, дислипидемия, инсулинорезистентность. В данной статье отображены особенности генов, способствующих развитию МС, а также клинические особенности течения данной патологии.

Recently, the role of metabolic syndrome (MS) has become crucial. There is a tendency for this disease to increase not only in the Russian Federation and throughout the world. According to World Health Organization data for 2022, approximately 60% of the European population is overweight or obese. The United States and Russia have the largest numbers of obese individuals. MS often occurs in developed countries, mainly in the adult population, and is a comorbid pathology. MS increases the risk of future disability and mortality. Despite the environmental factors that increase the risk of MS, genetic factors are also involved in the development of this pathology. The genes involved in the development of MS: MC4R, LEP, LEPR, PCSK1, ADCY3, POMC, and MRAP2, were identified. These genes and MRAP2 were identified and involved in the leptin-melanocortin signaling pathway, namely, they regulate energy metabolism, which, when a mutation occurs, leads to nonsyndromic monogenic obesity. MS is a multifactorial pathological condition that includes four independent sub-syndromes: obesity or overweight, hypertension, dyslipidemia, and insulin resistance. This article describes the features of genes contributing to the development of MS as well as the clinical features of the MS course.

метаболический синдроможирениегеныгенотипожирениеартериальная гипертензиядислипидемияинсулинорезистентностьmetabolic syndromeobesitygenesgenotypeobesityhypertensiondyslipidemiainsulin resistanceReferencesBoutari C, Mantzoros CS. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism. 2022 Aug;133:155217. https://doi.org/10.1016/j.metabol.2022.155217.Boutari C, Mantzoros CS. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism. 2022 Aug;133:155217. https://doi.org/10.1016/j.metabol.2022.155217.Timasheva YR, Balkhiyarova ZR, Kochetova OV. [Current state of the obesity research: genetic aspects, the role of microbiome, and susceptibility to COVID-19]. Probl Endokrinol (Mosk). 2021 Aug 2;67(4):20-35. Russian. https://doi.org/10.14341/probl12775.Timasheva YR, Balkhiyarova ZR, Kochetova OV. [Current state of the obesity research: genetic aspects, the role of microbiome, and susceptibility to COVID-19]. Probl Endokrinol (Mosk). 2021 Aug 2;67(4):20-35. Russian. https://doi.org/10.14341/probl12775.Vrdoljak J, Kumric M, Vilovic M, et al. Can Fasting Curb the Metabolic Syndrome Epidemic? Nutrients. 2022 Jan 20;14(3):456. https://doi.org/10.3390/nu14030456.Vrdoljak J, Kumric M, Vilovic M, et al. Can Fasting Curb the Metabolic Syndrome Epidemic? Nutrients. 2022 Jan 20;14(3):456. https://doi.org/10.3390/nu14030456.Niazi RK, Gjesing AP, Hollensted M, et al. Screening of 31 genes involved in monogenic forms of obesity in 23 Pakistani probands with earlyonset childhood obesity: a case report. BMC Med Genet. 2019 Sep 5;20(1):152. https://doi.org/10.1186/s12881-019-0886-8.Niazi RK, Gjesing AP, Hollensted M, et al. Screening of 31 genes involved in monogenic forms of obesity in 23 Pakistani probands with earlyonset childhood obesity: a case report. BMC Med Genet. 2019 Sep 5;20(1):152. https://doi.org/10.1186/s12881-019-0886-8.Киселева А.В., Мешков А.Н., Ершова А.И., и др. Генетика ожирения: современное состояние проблемы. Профилактическая медицина. 2021;24(12):89 96. https://doi.org/10.17116/profmed20212412189.Kiseleva AV, Meshkov AN, Ershova AI, et al. Obesity genetics: current state of the problem. Russian Journal of Preventive Medicine. 2021;24(12):89 96. (In Russ.). https://doi.org/10.17116/profmed20212412189.Алфёрова В.И., Мустафина С.В. Распространенность ожирения во взрослой популяции Российской Федерации (обзор литературы). Ожирение и метаболизм. 2022;19(1):96-105. https://doi.org/10.14341/omet12809.Alferova VI, Mustafina SV. The prevalence of obesity in the adult population of the Russian Federation (literature review). Obesity and metabolism. 2022;19(1):96-105. (In Russ.). https://doi.org/10.14341/omet12809.Осадчук М.А., Васильева И.Н., Козлов В.В., Митрохина О.И. Метаболический синдром как фактор риска онкогенеза. Профилактическая медицина. 2023;26(1):70 79. https://doi.org/10.17116/profmed20232601170.Osadchuk MA, Vasilieva IN, Kozlov VV, Mitrokhina OI. Metabolic syndrome as a risk factor for oncogenesis. Russian Journal of Preventive Medicine. 2023;26(1):70 79. (In Russ.). https://doi.org/10.17116/profmed20232601170.Mendonça PDS, Aguiar APN, Pinheiro RF, Magalhães SMM. Metabolic syndrome: A patient-related prognostic factor for cancer? J Cancer Res Ther. 2022 Jul-Sep;18(4):1210-1211. https://doi.org/10.4103/jcrt.JCRT_323_19.Mendonça PDS, Aguiar APN, Pinheiro RF, Magalhães SMM. Metabolic syndrome: A patient-related prognostic factor for cancer? J Cancer Res Ther. 2022 Jul-Sep;18(4):1210-1211. https://doi.org/10.4103/jcrt.JCRT_323_19.Шрайнер Е.В., Кох Н.В., Лифшиц Г.И. Ассоциация средовых факторов с избыточной массой тела и ожирением у детей дошкольного и младшего школьного возраста. Сибирский журнал клинической и экспериментальной медицины. 2021;36(3):148-153. https://doi.org/10.29001/2073-8552-2021-36-3-148-153.Shrayner EV, Kokh NV, Lifshits GI. Association of environmental factors with overweight and obesity in preschool and primary school children. Siberian Journal of Clinical and Experimental Medicine. 2021;36(3):148-153. (In Russ.). https://doi.org/10.29001/2073-8552-2021-36-3-148-153.Hainer V, Aldhoon Hainerová I, Kunešová M, et al. Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R). Physiol Res. 2020 Sep 30;69(Suppl 2):S245-S254. https://doi.org/10.33549/physiolres.934512.Hainer V, Aldhoon Hainerová I, Kunešová M, et al. Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R). Physiol Res. 2020 Sep 30;69(Suppl 2):S245-S254. https://doi.org/10.33549/physiolres.934512.Wu Q, Li J, Sun X, et al. Multi-stage metabolomics and genetic analyses identified metabolite biomarkers of metabolic syndrome and their genetic determinants. EBioMedicine. 2021 Dec;74:103707. https://doi.org/10.1016/j.ebiom.2021.103707.Wu Q, Li J, Sun X, et al. Multi-stage metabolomics and genetic analyses identified metabolite biomarkers of metabolic syndrome and their genetic determinants. EBioMedicine. 2021 Dec;74:103707. https://doi.org/10.1016/j.ebiom.2021.103707.Berger C, Klöting N. Leptin Receptor Compound Heterozygosity in Humans and Animal Models. Int J Mol Sci. 2021 Apr 25;22(9):4475. https://doi.org/10.3390/ijms22094475.Berger C, Klöting N. Leptin Receptor Compound Heterozygosity in Humans and Animal Models. Int J Mol Sci. 2021 Apr 25;22(9):4475. https://doi.org/10.3390/ijms22094475.Mohammed I, Selvaraj S, Ahmed WS, et al. Functional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar. Int J Mol Sci. 2023 Nov 15;24(22):16361. https://doi.org/10.3390/ijms242216361.Mohammed I, Selvaraj S, Ahmed WS, et al. Functional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar. Int J Mol Sci. 2023 Nov 15;24(22):16361. https://doi.org/10.3390/ijms242216361.Yang Y, Gao X, Tao X, et al. Combined effect of FTO and MC4R gene polymorphisms on obesity in children and adolescents in Northwest China: a case-control study. Asia Pac J Clin Nutr. 2019;28(1):177-182. https://doi.org/10.6133/apjcn.201903_28(1).0023.Yang Y, Gao X, Tao X, et al. Combined effect of FTO and MC4R gene polymorphisms on obesity in children and adolescents in Northwest China: a case-control study. Asia Pac J Clin Nutr. 2019;28(1):177-182. https://doi.org/10.6133/apjcn.201903_28(1).0023.Batarfi AA, Filimban N, Bajouh OS, et al. MC4R variants rs12970134 and rs17782313 are associated with obese polycystic ovary syndrome patients in the Western region of Saudi Arabia. BMC Med Genet. 2019 Aug 20;20(1):144. https://doi.org/10.1186/s12881-019-0876-x.Batarfi AA, Filimban N, Bajouh OS, et al. MC4R variants rs12970134 and rs17782313 are associated with obese polycystic ovary syndrome patients in the Western region of Saudi Arabia. BMC Med Genet. 2019 Aug 20;20(1):144. https://doi.org/10.1186/s12881-019-0876-x.Тимашева Я.Р., Балхиярова Ж.Р., Кочетова О.В. Современное состояние исследований в области ожирения: генетические аспекты, роль микробиома и предрасположенность к COVID-19. Проблемы Эндокринологии. 2021;67(4):20-35. https://doi.org/10.14341/probl12775.Timasheva YaR, Balkhiyarova ZhR, Kochetova OV. Current state of the obesity research: genetic aspects, the role of microbiome, and susceptibility to COVID-19. Problems of Endocrinology. 2021;67(4):20-35. (In Russ.). https://doi.org/10.14341/probl12775.Van Dijck E, Beckers S, Diels S, et al. Rare Heterozygous PCSK1 Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review. Genes (Basel). 2022 Sep 27;13(10):1746. https://doi.org/10.3390/genes13101746.Van Dijck E, Beckers S, Diels S, et al. Rare Heterozygous PCSK1 Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review. Genes (Basel). 2022 Sep 27;13(10):1746. https://doi.org/10.3390/genes13101746.Toumba M, Fanis P, Vlachakis D, et al. Molecular modelling of novel ADCY3 variant predicts a molecular target for tackling obesity. Int J Mol Med. 2022 Jan;49(1):10. https://doi.org/10.3892/ijmm.2021.5065.Toumba M, Fanis P, Vlachakis D, et al. Molecular modelling of novel ADCY3 variant predicts a molecular target for tackling obesity. Int J Mol Med. 2022 Jan;49(1):10. https://doi.org/10.3892/ijmm.2021.5065.Bernard A, Ojeda Naharros I, Yue X, et al. MRAP2 regulates energy homeostasis by promoting primary cilia localization of MC4R. JCI Insight. 2023 Jan 24;8(2):e155900. https://doi.org/10.1172/jci.insight.155900.Bernard A, Ojeda Naharros I, Yue X, et al. MRAP2 regulates energy homeostasis by promoting primary cilia localization of MC4R. JCI Insight. 2023 Jan 24;8(2):e155900. https://doi.org/10.1172/jci.insight.155900.Castro-Barquero S, Ruiz-León AM, Sierra-Pérez M, Estruch R, Casas R. Dietary Strategies for Metabolic Syndrome: A Comprehensive Review. Nutrients. 2020 Sep 29;12(10):2983. https://doi.org/10.3390/nu12102983.Castro-Barquero S, Ruiz-León AM, Sierra-Pérez M, Estruch R, Casas R. Dietary Strategies for Metabolic Syndrome: A Comprehensive Review. Nutrients. 2020 Sep 29;12(10):2983. https://doi.org/10.3390/nu12102983.da Silva Rosa SC, Nayak N, Caymo AM, Gordon JW. Mechanisms of muscle insulin resistance and the cross-talk with liver and adipose tissue. Physiol Rep. 2020 Oct;8(19):e14607. https://doi.org/10.14814/phy2.14607.da Silva Rosa SC, Nayak N, Caymo AM, Gordon JW. Mechanisms of muscle insulin resistance and the cross-talk with liver and adipose tissue. Physiol Rep. 2020 Oct;8(19):e14607. https://doi.org/10.14814/phy2.14607.Fahed G, Aoun L, Bou Zerdan M, et al. Metabolic Syndrome: Updates on Pathophysiology and Management in 2021. Int J Mol Sci. 2022 Jan 12;23(2):786. https://doi.org/10.3390/ijms23020786.Fahed G, Aoun L, Bou Zerdan M, et al. Metabolic Syndrome: Updates on Pathophysiology and Management in 2021. Int J Mol Sci. 2022 Jan 12;23(2):786. https://doi.org/10.3390/ijms23020786.Cho Y, Lee SY. Useful Biomarkers of Metabolic Syndrome. Int J Environ Res Public Health. 2022 Nov 15;19(22):15003. https://doi.org/10.3390/ijerph192215003.Cho Y, Lee SY. Useful Biomarkers of Metabolic Syndrome. Int J Environ Res Public Health. 2022 Nov 15;19(22):15003. https://doi.org/10.3390/ijerph192215003.Танянский Д.А., Денисенко А.Д. Влияние адипонектина на обмен углеводов, липидов и липопротеинов: анализ сигнальных механизмов. Ожирение и метаболизм. 2021;18(2):103-111. https://doi.org/10.14341/omet12754Tanyanskiy DA, Denisenko AD. The influence of adiponectin on carbohydrates, lipids, and lipoproteins metabolism: analysis of signaling mechanisms. Obesity and metabolism. 2021;18(2):103-111. (In Russ.). https://doi.org/10.14341/omet12754Кох Н.В., Шрайнер Е.В., Воронина Е.Н., и др. Изучение ассоциации полиморфных локусов rs5400 гена SLC2A2 (GLUT2) и rs4684677 гена GHRL с избыточной массой тела и предпочтением углеводов у детей дошкольного и младшего школьного возраста. Российский педиатрический журнал. 2021;2(1):20-27. https://doi.org/10.15690/rpj.v2i1.2189.Kokh NV, Schreiner EV, Voronina EN, et al. Study of association of the rs5400 polymorphic locus in the SLC2A2 (GLUT2) gene and the rs4684677 polymorphic locus in the GHRL gene with excess body weight and preference for carbohydrates in preschool and primary school-aged children. Russian Pediatric Journal. 2021;2(1):20-27. (In Russ.). https://doi.org/10.15690/rpj.v2i1.2189.Морозова Т.Е., Воробьева О.В., Герцог А.А. Хронический болевой синдром и ожирение: ассоциации маркеров воспаления с характеристиками болевого синдрома. Лечащий Врач. 2023;(2):7-11. https://doi.org/10.51793/OS.2023.26.2.001.Morozova TE, Vorob'eva OV, Gertsog AA. Chronic pain syndrome and obesity: associations of inflammatory markers with pain characteristics. Lechaschi Vrach. 2023;(2):7-11. (In Russ.). https://doi.org/10.51793/OS.2023.26.2.001.Кузина И.А., Гончарова Е.В., Мартиросян Н.С. и др. Состояние гемостаза у женщин с ожирением и метаболическим синдромом. РМЖ. Медицинское обозрение. 2021;5(9):598-604. https://doi.org/10.32364/2587-6821-2021-5-9-598-604.Kuzina IA, Goncharova EV, Martirosyan NS, et al. Hemostasis in women with obesity and metabolic syndrome. Russian Medical Inquiry. 2021;5(9):598-604. (In Russ.). https://doi.org/10.32364/2587-6821-2021-5-9-598-604.Karra P, Winn M, Pauleck S, et al. Metabolic dysfunction and obesityrelated cancer: Beyond obesity and metabolic syndrome. Obesity (Silver Spring). 2022 Jul;30(7):1323-1334. https://doi.org/10.1002/oby.23444.Karra P, Winn M, Pauleck S, et al. Metabolic dysfunction and obesityrelated cancer: Beyond obesity and metabolic syndrome. Obesity (Silver Spring). 2022 Jul;30(7):1323-1334. https://doi.org/10.1002/oby.23444.Heyn GS, Corrêa LH, Magalhães KG. The Impact of Adipose TissueDerived miRNAs in Metabolic Syndrome, Obesity, and Cancer. Front Endocrinol (Lausanne). 2020 Oct 6;11:563816. https://doi.org/10.3389/fendo.2020.563816.Heyn GS, Corrêa LH, Magalhães KG. The Impact of Adipose TissueDerived miRNAs in Metabolic Syndrome, Obesity, and Cancer. Front Endocrinol (Lausanne). 2020 Oct 6;11:563816. https://doi.org/10.3389/fendo.2020.563816.Обрезан А.Г., Щербакова Н.В. Патогенетические механизмы развития патологии миокарда у больных со злокачественными новообразованиями: современное состояние проблемы. Кардиология. 2020;60(2):142-154. https://doi.org/10.18087/cardio.2020.2.n985.Obrezan A.G., Shcherbakova N.V. Pathogenetic mechanisms of development of myocardial pathology in patients with malignant tumors: the current state of the problem. Kardiologiia. 2020;60(2):142-154. (In Russ.). https://doi.org/10.18087/cardio.2020.2.n985.Ali Syeda Z, Langden SSS, Munkhzul C, et al. Regulatory Mechanism of MicroRNA Expression in Cancer. Int J Mol Sci. 2020 Mar 3;21(5):1723. https://doi.org/10.3390/ijms21051723.Ali Syeda Z, Langden SSS, Munkhzul C, et al. Regulatory Mechanism of MicroRNA Expression in Cancer. Int J Mol Sci. 2020 Mar 3;21(5):1723. https://doi.org/10.3390/ijms21051723.Миронова О.Ю., Бердышева М.В., Елфимова Е.М. МикроРНК: взгляд клинициста на состояние проблемы. Часть 1. История вопроса. Евразийский кардиологический журнал. 2023;(1):100-107. https://doi.org/10.38109/2225-1685-2023-1-100-107.Mironova OIu, Berdysheva MV, Elfimova EM. MicroRNA: a clinician’s view of the state of the problem. Part 1. History of the issue. Eurasian heart journal. 2023;(1): 100-107. (In Russ.). https://doi.org/10.38109/2225-1685-2023-1-100-107.

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