arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2025-2513JWMLNFarthyper-2513Research ArticleСтатьиArticlesВарианты гена рецептора витамина D и экспрессия микроРНК‑21, микроРНК‑125а, микроРНК‑125b и микроРНК‑214 у больных ишемической болезнью сердцаVariants of the vitamin D receptor gene and the expression of microRNA‑21, microRNA‑125a, microRNA‑125b and microRNA‑214 in coronary heart diseasehttps://orcid.org/0000-0001-5795-4006ИоноваЖ. И.IonovaZ. I.

Ионова Жанна Игоревна — кандидат медицинских наук, доцент кафедры терапии факультетской с курсом эндокринологии и кардиологии с клиникой им. акад. Г. Ф. Ланга

ул. Льва Толстого, 6/8, Санкт-Петербург, 197022

Zhanna I. Ionova, MD, PhD, Associate Professor, Department of Therapy # 2 with a Course in Endocrinology and Cardiology at the Clinic Named after Academician G. F. Lang

6/8 Lev Tolstoy str., St Petersburg, 197022

zhanna@ncmed.mehttps://orcid.org/0000-0002-5358-5968БерковичО. А.BerkovichO. A.

Беркович Ольга Александровна — доктор медицинских наук, профессор кафедры терапии факультетской с курсом эндокринологии и кардиологии с клиникой им. акад. Г. Ф. Ланга

ул. Льва Толстого, 6/8, Санкт-Петербург, 197022

Olga A. Berkovich, MD, PhD, DSc, Professor, Department of Therapy # 2 with a Course in Endocrinology and Cardiology at the Clinic Named after Academician G. F. Lang

6/8 Lev Tolstoy str., St Petersburg, 197022

oberkovich@mail.ruhttps://orcid.org/0000-0002-5349-2227БеляеваО. Д.BelyaevaO. D.

Беляева Ольга Дмитриевна — доктор медицинских наук, профессор кафедры терапии факультетской с курсом эндокринологии и кардиологии с клиникой им. акад. Г. Ф. Ланга

ул. Льва Толстого, 6/8, Санкт-Петербург, 197022

Olga D. Belyaeva, MD, PhD, DSc, Professor, Department of Therapy # 2 with a Course in Endocrinology and Cardiology at the Clinic Named after Academician G. F. Lang

6/8 Lev Tolstoy str., St Petersburg, 197022

olgad.bel@gmail.comhttps://orcid.org/0000-0002-7605-4369ЗарайскийМ. И.ZaraiskyM. I.

Зарайский Михаил Игоревич — доктор медицинских наук, профессор кафедры медицинской генетики СЗГМУ имени И. И. Мечникова, заведующий лабораторией молекулярной диагностики НМЦ РФ по молекулярной медицине

Санкт-Петербург

Mikhail I. Zaraisky, MD, PhD, DSc, Professor, Department of Medical Genetics, I. I. Mechnikov Northwestern State Medical University, Head, Laboratory of Molecular Diagnostics, Russian Federation National Medical Center for Molecular Medicine

St Petersburg

mzaraiski@yandex.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова» Минздрава РоссииРоссияPavlov UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Северо-Западный государственный медицинский университет им. И. И. Мечникова» Минздрава РоссииРоссияNorth-Western State Medical University named after I. I. MechnikovRussian Federation202520082025313224237Copyright © Ионова Ж.И., Беркович О.А., Беляева О.Д., Зарайский М.И., 20252025Ионова Ж.И., Беркович О.А., Беляева О.Д., Зарайский М.И.Ionova Z.I., Berkovich O.A., Belyaeva O.D., Zaraisky M.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/2513

Актуальность. Защитные эффекты витамина D в отношении атерогенеза реализуются за счет рецепторов витамина D (VDR). Варианты rs10735810, rs731236, rs1544410 и rs797532 гена VDR вовлечены в регуляцию стабильности его мРНК. МикроРНК‑214, микроРНК‑125а, микроРНК‑125b и микроРНК‑21 связываются с 3’регуляторным доменом гена VDR и влияют на экспрессию белка VDR.Цель исследования - оценить уровни экспрессии микроРНК‑214, микроРНК‑125а, микроРНК‑125b, микроРНК‑21 у больных ишемической болезнью сердца (ИБС) с rs10735810, rs731236, rs1544410 и rs797532 вариантами гена VDR.Материалы и методы. Генотипы гена VDR определены у 766 больных ИБС и у 336 человек без ИБС (группа сравнения) методом полимеразной цепной реакции (ПЦР) с последующим рестрикционным анализом. Экспрессия микроРНК определялась методом ПЦР в реальном времени.Результаты. Генотипы ff, Ff и аллель f гена VDR (rs10735810) чаще выявлялись у больных ИБС, чем в группе сравнения (p = 0,001, р = 0,03 и р = 0,047 соответственно). Носительство генотипа ff (rs10735810) гена VDR ассоциировано с повышением риска развития ИБС (отношение шансов (OШ) = 1,80; 95 %-ный доверительный интервал (ДИ): 1,30÷2,50, р = 0,0004). Генотип аа гена VDR (rs797532) и bb генотип гена VDR (rs1544410) встречались чаще у больных ИБС, чем в группе сравнения (p = 0,008 и р = 0,001). Наличие генотипов аа и bb гена VDR было связано с повышением риска развития ИБС (ОШ = 1,50; 95 % ДИ:1,11÷2,02, p = 0,008, ОШ = 1,77; 95 % ДИ: 1,35÷2,32, р = 0,001 соответственно). Уровни экспрессии микроРНК‑214, микроРНК‑125а, микроРНК‑125b и микроРНК‑21 в крови выше у больных ИБС, чем в группе сравнения (р < 0,001). Экспрессия микроРНК‑125а была выше у курящих пациентов, чем у некурящих (59,85 (21,69; 73,06) условных единиц экспрессии (УЕЭ) и 32,00 (4,59; 67,85) УЕЭ соответственно; р = 0,04). У больных ИБС, имеющих Tt генотип гена VDR (rs731236), экспрессия микроРНК‑214 выше, чем у но- сителей tt генотипа гена VDR (р = 0,03). У больных ИБС с аа генотипом гена VDR (rs797532) экспрессия микроРНК‑214, микроРНК‑125а, микроРНК‑125b и микроРНК‑21 в крови выше, чем у пациентов с АА генотипом гена VDR (р < 0,05). Экспрессия микроРНК‑125а, микроРНК‑125b и микроРНК‑21 в крови больных ИБС, носителей bb генотипа гена VDR (rs1544410), выше, чем у имеющих BB генотип гена VRD (р < 0,05).Заключение. МикроРНК‑214, микроРНК‑125a, микроРНК‑125b и микроРНК‑21, генотипы aa, ff, bb гена VDR (rs797532, rs10735810 и rs1544410 варианты) представляют собой перспективные маркеры ИБС. Варианты гена VDR могут оказывать влияние на уровни экспрессии микроРНК‑214, микроРНК‑125a, микроРНК‑125b и микроРНК‑21.

Background. The protective effects of vitamin D in relation to atherogenesis are realized by vitamin D receptors (VDR). Variants rs10735810, rs731236, rs1544410 and rs797532 of the VDR gene are involved in regulating the stability of its mRNA. МicroRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21 bind to the 3’regulatory domain of the VDR gene and affect VDR protein expression.Оbjective. To evaluate the expression levels of microRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21 in coronary heart disease (CHD) patients with rs10735810, rs731236, rs1544410 and rs797532 variants of the VDR gene.Design and methods. The genotypes of the VDR gene were determined in 766 CHD patients and in 336 people without CHD (comparison group) by polymerase chain reaction (PCR) followed by restriction analysis. MicroRNA expression was determined by real-time PCR.Results. The ff, Ff genotypes and the f allele of the VDR gene (rs10735810) were more often detected in CHD patients than in the comparison group (p = 0,001, p = 0,03 and p = 0,047, respectively). Carriage of the ff (rs10735810) genotype of the VDR gene was associated with an increased risk of CHD (odds ratio (OR) = 1,80; 95 % confidence interval (CI): 1,30–2,50, p = 0,0004). The aa genotype of the VDR gene (rs797532) and the bb genotype of the VDR gene (rs1544410) were more common in CHD patients than in the comparison group (p = 0,008 and p = 0,001). The presence of the aa and bb genotypes of the VDR gene was associated with an increased risk of CHD (OR = 1,50; 95 % CI: 1,11÷2,02, p = 0,008, OR = 1,77; 95 % CI: 1,35÷2,32, p = 0,001, respectively). The expression levels of microRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21 in the blood are higher in CHD patients than in the control group (p < 0,001). The expression of microRNA‑125a was higher in smoking patients than in non-smokers (59,85 (21,69; 73,06) conventional units of expression (UE) and 32,00 (4,59; 67,85) UE, respectively; p = 0,04). In CHD patients with Tt genotype of the VDR gene (rs731236), the expression of microRNA‑214 is higher than in carriers of the tt genotype of the VDR gene (p = 0,03). In CHD patients with the aa genotype of the VDR gene (rs797532), the expression of microRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21 in the blood is higher than in patients with the AA genotype of the VDR gene (p < 0,05). The expression of microRNA‑125a, microRNA‑125b and microRNA‑21 in the blood of CHD patients, carriers of the bb genotype of the VDR gene (rs1544410), is higher than in those with the BB genotype of the VDR gene (p < 0,05). Conclusion. MicroRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21, genotypes aa, ff and bb of the VDR gene (rs797532, rs10735810, and rs1544410 variants), represent promising markers of CHD. Variants of the VDR gene can affect the expression levels of microRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21.

рецептор витамина Dишемическая болезнь сердцамикроРНК‑214микроРНК‑125амикроРНК‑125bмикроРНК‑21coronary heart diseasevitamin D receptormicroRNA‑21microRNA‑125amicroRNA‑125bmicroRNA‑214Госзадание No АААА-А18-118070690073-2 «Сердечно-сосудистые заболевания при ожирении: молекулярно-генетические предикторы развития, прогрессировали и подходы к лечению».ReferencesKnuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al.; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407–477. https://doi.org/10.1093/eurheartj/ehz425Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al.; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407–477. https://doi.org/10.1093/eurheartj/ehz425Национальный проект «Здравоохранение» // ОРГЗДРАВ: Новости. Мнения. Обучение. Вестник ВШОУЗ. 2018;3(13). Доступно по: https://cyberleninka.ru/article/n/natsionalnyy-proektzdravoohranenieNational Healthcare Project // ORGZDRAV: News. Opinions. Training. Bulletin of the VSHOUZ. 2018;3(13). (In Russ.) Available at: https://cyberleninka.ru/article/n/natsionalnyy-proektzdravoohranenieO’Sullivan JW, Ashley EA, Elliott PM. Polygenic risk scores for the prediction of cardiometabolic disease. Eur Heart J. 2023;44(2):89–99. https://doi.org/10.1093/eurheartj/ehac648O’Sullivan JW, Ashley EA, Elliott PM. Polygenic risk scores for the prediction of cardiometabolic disease. Eur Heart J. 2023;44(2):89–99. https://doi.org/10.1093/eurheartj/ehac648Semaev S, Shakhtshneider E. Genetic risk score for coronary heart disease: review. J Pers Med. 2020;10(4):239. https://doi.org/10.3390/jpm10040239Semaev S, Shakhtshneider E. Genetic risk score for coronary heart disease: review. J Pers Med. 2020;10(4):239. https://doi.org/10.3390/jpm10040239Yan X, Wei Y, Wang D, Zhao J, Zhu K, Liu Y, et al. Four common vitamin D receptor polymorphisms and coronary artery disease susceptibility: A trial sequential analysis. PLoS One. 2022;17(10):e0275368. https://doi.org/10.1371/journal.pone.0275368Yan X, Wei Y, Wang D, Zhao J, Zhu K, Liu Y, et al. Four common vitamin D receptor polymorphisms and coronary artery disease susceptibility: A trial sequential analysis. PLoS One. 2022;17(10):e0275368. https://doi.org/10.1371/journal.pone.0275368Donda KT, Torres BA, Khashu M, Maheshwari A. Single nucleotide polymorphisms in neonatal necrotizing enterocolitis. Curr Pediatr Rev. 2022;18(3):197–209. https://doi.org/10.2174/1573396318666220117091621Donda KT, Torres BA, Khashu M, Maheshwari A. Single nucleotide polymorphisms in neonatal necrotizing enterocolitis. Curr Pediatr Rev. 2022;18(3):197–209. https://doi.org/10.2174/1573396318666220117091621Alimardani M, Moghbeli M, Rastgar-Moghadam A, Shandiz FH, Abbaszadegan MR. Single nucleotide polymorphisms as the efficient prognostic markers in breast cancer. Curr Cancer Drug Targets. 2021;21(9):768–793. https://doi.org/10.2174/1568009621666210525151846Alimardani M, Moghbeli M, Rastgar-Moghadam A, Shandiz FH, Abbaszadegan MR. Single nucleotide polymorphisms as the efficient prognostic markers in breast cancer. Curr Cancer Drug Targets. 2021;21(9):768–793. https://doi.org/10.2174/1568009621666210525151846Xiao M, Yang S, Zhou A, Li T, Liu J, Chen Y, et al. MiR‑27a‑3p and miR‑30b‑5p inhibited-vitamin D receptor involved in the progression of tuberculosis. Front Microbiol. 2022;13: 1020542. https://doi.org/10.3389/fmicb.2022.1020542Xiao M, Yang S, Zhou A, Li T, Liu J, Chen Y, et al. MiR‑27a‑3p and miR‑30b‑5p inhibited-vitamin D receptor involved in the progression of tuberculosis. Front Microbiol. 2022;13: 1020542. https://doi.org/10.3389/fmicb.2022.1020542Chen YT, Wong LL, Liew OW, Richards AM. Heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF): The diagnostic value of circulating MicroRNAs. Cells. 2019;8(12):1651. https://doi.org/10.3390/cells8121651Chen YT, Wong LL, Liew OW, Richards AM. Heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF): The diagnostic value of circulating MicroRNAs. Cells. 2019;8(12):1651. https://doi.org/10.3390/cells8121651Aonuma T, Moukette B, Kawaguchi S, Barupala NP, Sepúlveda MN, Frick K, et al. MiR‑150 attenuates maladaptive cardiac remodeling mediated by long noncoding RNA MIAT and directly represses profibrotic Hoxa4. Circ Heart Fail. 2022;15(4): e008686. https://doi.org/10.1161/CIRCHEARTFAILURE.121.008686Aonuma T, Moukette B, Kawaguchi S, Barupala NP, Sepúlveda MN, Frick K, et al. MiR‑150 attenuates maladaptive cardiac remodeling mediated by long noncoding RNA MIAT and directly represses profibrotic Hoxa4. Circ Heart Fail. 2022;15(4): e008686. https://doi.org/10.1161/CIRCHEARTFAILURE.121.008686Zhou Q, Luo L, Wang X, Li X. Relationship between single nucleotide polymorphisms in the 3’UTR of amyloid precursor protein and risk of Alzheimer’s disease and its mechanism. Biosci Rep. 2019;39(5): BSR20182485. https://doi.org/10.1042/BSR20182485Zhou Q, Luo L, Wang X, Li X. Relationship between single nucleotide polymorphisms in the 3’UTR of amyloid precursor protein and risk of Alzheimer’s disease and its mechanism. Biosci Rep. 2019;39(5): BSR20182485. https://doi.org/10.1042/BSR20182485Lozano-Velasco E, Inácio JM, Sousa I, Guimarães AR, Franco D, Moura G, et al. miRNAs in heart development and disease. Int J Mol Sci. 2024;25(3):1673. https://doi.org/10.3390/ijms25031673Lozano-Velasco E, Inácio JM, Sousa I, Guimarães AR, Franco D, Moura G, et al. miRNAs in heart development and disease. Int J Mol Sci. 2024;25(3):1673. https://doi.org/10.3390/ijms25031673Siasos G, Bletsa E, Stampouloglou PK, Oikonomou E, Tsigkou V, Paschou SA, et al. MicroRNAs in cardiovascular disease. Hellenic J Cardiol. 2020;61(3):165–173. https://doi.org/10.1016/j.hjc.2020.03.003Siasos G, Bletsa E, Stampouloglou PK, Oikonomou E, Tsigkou V, Paschou SA, et al. MicroRNAs in cardiovascular disease. Hellenic J Cardiol. 2020;61(3):165–173. https://doi.org/10.1016/j.hjc.2020.03.003Mohri T, Nakajima M, Takagi S. MicroRNA regulates human vitamin D receptor. Int J Cancer. 2009;125(6):1328–33. https://doi.org/doi:10.1002/ijc.24459Mohri T, Nakajima M, Takagi S. MicroRNA regulates human vitamin D receptor. Int J Cancer. 2009;125(6):1328–33. https://doi.org/doi:10.1002/ijc.24459Lisse TS, Adams JS, Hewison M. Vitamin D and MicroRNAs in bone. Crit Rev Eukaryot Gene Expr. 2013;23(3):195–214. https://doi.org/10.1615/critreveukaryotgeneexpr.2013007147Lisse TS, Adams JS, Hewison M. Vitamin D and MicroRNAs in bone. Crit Rev Eukaryot Gene Expr. 2013;23(3):195–214. https://doi.org/10.1615/critreveukaryotgeneexpr.2013007147Беляева О. Д., Ду Ц., Ионова Ж. И., Каронова Т. Л., Полуничева Е. В., Мирошникова В. В. и др. Тяжесть поражения коронарных артерий у больных ишемической болезнью сердца с различными вариантами гена рецептора витамина D и уровнем обеспеченности витамином D. Ученые записки ПСПбГМУ им. акад. И. П. Павлова. 2022;29(2):41–51. https://doi.org/10.24884/1607-4181-2022-29-2-41-51Belyaeva OD, Du J, Ionova ZhI, Karonova TL, Polunicheva EV, Miroshnikova VV, et al. The severity of coronary artery defeat in coronary heart disease patients with different variants of the vitamin D receptor gene and the level of vitamin D sufficiency. The Scientific Notes of Pavlov University. 2022;29(2):41–51. (In Russ.) https://doi.org/10.24884/1607-4181-2022-29-2-41-51Реброва О. Ю. Статистический анализ медицинских данных. Применение пакета прикладных программ STATISTICA. М.: МедиаСфера, 2000. 312 с.Rebrova OYu. Statistical analysis of medical data. Application of the STATISTICA application package. Moscow: MediaSfera, 2000. 312 p. (In Russ.)Кириллова Г. Н., Никитина С. Ю., Харькова Т. Л., Чумарина В. Ж., Смелов П. А., Агеева Л. И. и др. Здравоохранение в России. 2021. Москва: Стат.сб./Росстат, 2021. 171 c.Kirillova GN, Nikitina SYu, Kharkova TL, Chumarina VZh, Smelov PA, Ageeva LI, et al. Healthcare in Russia. 2021. Moscow: Stat.sb./Rosstat, 2021. 171 p. (In Russ.)McPherson R, Tybjaerg-Hansen A. Genetics of coronary artery disease. Circ Res. 2016;118(4):564–578. https://doi.org/10.1161/CIRCRESAHA.115.306566McPherson R, Tybjaerg-Hansen A. Genetics of coronary artery disease. Circ Res. 2016;118(4):564–578. https://doi.org/10.1161/CIRCRESAHA.115.306566Abouzid M, Kruszyna M, Burchardt P, Kruszyna Ł, Główka FK, Karaźniewicz-Łada M. Vitamin D receptor gene polymorphism and vitamin D status in population of patients with cardiovascular disease — a preliminary study. Nutrients. 2021;13(9):3117. https://doi.org/10.3390/nu13093117Abouzid M, Kruszyna M, Burchardt P, Kruszyna Ł, Główka FK, Karaźniewicz-Łada M. Vitamin D receptor gene polymorphism and vitamin D status in population of patients with cardiovascular disease — a preliminary study. Nutrients. 2021;13(9):3117. https://doi.org/10.3390/nu13093117Tabaei S, Motallebnezhad M, Tabaee SS. Vitamin D receptor (VDR) gene polymorphisms and risk of coronary artery disease (CAD): systematic review and meta-analysis. Biochem Genet. 2021;59(4):813–836. https://doi.org/10.1007/s10528–021–10038‑x21 Tabaei S, Motallebnezhad M, Tabaee SS. Vitamin D receptor (VDR) gene polymorphisms and risk of coronary artery disease (CAD): systematic review and meta-analysis. Biochem Genet. 2021;59(4):813–836. https://doi.org/10.1007/s10528–021–10038‑xHe L, Wang M. Association of vitamin D receptor — a gene polymorphisms with coronary heart disease in Han Chinese. Int J Clin Exp Med. 2015;8(4):6224–9.He L, Wang M. Association of vitamin D receptor — a gene polymorphisms with coronary heart disease in Han Chinese. Int J Clin Exp Med. 2015;8(4):6224–9.Lu S, Guo S, Hu F, Guo Y, Yan L, Ma W, et al. The associations between the polymorphisms of vitamin D receptor and coronary artery disease: a systematic review and meta-analysis. Medicine (Baltimore). 2016;95(21): e3467. https://doi.org/10.1097/MD.0000000000003467Lu S, Guo S, Hu F, Guo Y, Yan L, Ma W, et al. The associations between the polymorphisms of vitamin D receptor and coronary artery disease: a systematic review and meta-analysis. Medicine (Baltimore). 2016;95(21): e3467. https://doi.org/10.1097/MD.0000000000003467Karam ZM, Yari A, Najmadini A, Khorasani NN, Attari R, Jafarinejad-Farsangi S, et al. Association of the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) polymorphisms with risk of coronary artery disease in Iranian patients. J Clin Lab Anal. 2024;38(6): e25026. https://doi.org/10.1002/jcla.25026Karam ZM, Yari A, Najmadini A, Khorasani NN, Attari R, Jafarinejad-Farsangi S, et al. Association of the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) polymorphisms with risk of coronary artery disease in Iranian patients. J Clin Lab Anal. 2024;38(6): e25026. https://doi.org/10.1002/jcla.25026Raljević D, Peršić V, Markova-Car E, Cindrić L, Miškulin R, Žuvić M, Kraljević Pavelić S. Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease. BMC Cardiovasc Disord. 2021;21(1):188. https://doi.org/10.1186/s12872–021–01959‑xRaljević D, Peršić V, Markova-Car E, Cindrić L, Miškulin R, Žuvić M, Kraljević Pavelić S. Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease. BMC Cardiovasc Disord. 2021;21(1):188. https://doi.org/10.1186/s12872–021–01959‑xFronczek M, Strzelczyk JK, Osadnik T, Biernacki K, Ostrowska Z. VDR gene polymorphisms in healthy individuals with family history of premature coronary artery disease. Dis Markers. 2021;2021:8832478. https://doi.org/10.1155/2021/8832478Fronczek M, Strzelczyk JK, Osadnik T, Biernacki K, Ostrowska Z. VDR gene polymorphisms in healthy individuals with family history of premature coronary artery disease. Dis Markers. 2021;2021:8832478. https://doi.org/10.1155/2021/8832478Akhlaghi B, Firouzabadi N, Foroughinia F, Nikparvar M, Dehghani P. Impact of vitamin D receptor gene polymorphisms (TaqI and BsmI) on the incidence and severity of coronary artery disease: a report from southern Iran. BMC Cardiovasc Disord. 2023;23(1):113. https://doi.org/10.1186/s12872-023-03155-5Akhlaghi B, Firouzabadi N, Foroughinia F, Nikparvar M, Dehghani P. Impact of vitamin D receptor gene polymorphisms (TaqI and BsmI) on the incidence and severity of coronary artery disease: a report from southern Iran. BMC Cardiovasc Disord. 2023;23(1):113. https://doi.org/10.1186/s12872-023-03155-5Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013;88(7):720–55. https://doi.org/10.1016/j.mayocp.2013.05.011Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013;88(7):720–55. https://doi.org/10.1016/j.mayocp.2013.05.011Torres-Paz YE, Gamboa R, Fuentevilla- Álvarez G, Soto ME, González-Moyotl N, Martínez-Alvarado R, et al. Overexpression of microRNA‑21–5p and microRNA‑221-5p in monocytes increases the risk of developing coronary artery disease. Int J Mol Sci. 2023;24(10):8641. https://doi.org/10.3390/ijms24108641Torres-Paz YE, Gamboa R, Fuentevilla- Álvarez G, Soto ME, González-Moyotl N, Martínez-Alvarado R, et al. Overexpression of microRNA‑21–5p and microRNA‑221-5p in monocytes increases the risk of developing coronary artery disease. Int J Mol Sci. 2023;24(10):8641. https://doi.org/10.3390/ijms24108641Nappi F, Avtaar Singh SS, Jitendra V, Alzamil A, Schoell T. The roles of microRNAs in the cardiovascular system. Int J Mol Sci. 2023;24(18):14277. https://doi.org/10.3390/ijms241814277Nappi F, Avtaar Singh SS, Jitendra V, Alzamil A, Schoell T. The roles of microRNAs in the cardiovascular system. Int J Mol Sci. 2023;24(18):14277. https://doi.org/10.3390/ijms241814277Holland A, Enrick M, Diaz A, Yin L. Is miR‑21 A therapeutic target in cardiovascular disease? Int J Drug Discov Pharm. 2023;2(1):26–36. https://doi.org/10.53941/ijddp.0201003Holland A, Enrick M, Diaz A, Yin L. Is miR‑21 A therapeutic target in cardiovascular disease? Int J Drug Discov Pharm. 2023;2(1):26–36. https://doi.org/10.53941/ijddp.0201003Mayr M, Zampetaki A, Willeit P, Willeit J, Kiechl S. MicroRNAs within the continuum of postgenomics biomarker discovery. Arterioscler Thromb Vasc Biol. 2013;33(2):206–14. https://doi.org/10.1161/ATVBAHA.112.300141Mayr M, Zampetaki A, Willeit P, Willeit J, Kiechl S. MicroRNAs within the continuum of postgenomics biomarker discovery. Arterioscler Thromb Vasc Biol. 2013;33(2):206–14. https://doi.org/10.1161/ATVBAHA.112.300141Wang D, Deuse T, Stubbendorff M, Chernogubova E, Erben RG, Eken SM, et al. Local MicroRNA modulation using a novel anti-mir‑21‑eluting stent effectively prevents experimental in-stent restenosis. Arterioscler Thromb Vasc Biol. 2015;35(9):1945–53. https://doi.org/10.1161/ATVBAHA.115.305597Wang D, Deuse T, Stubbendorff M, Chernogubova E, Erben RG, Eken SM, et al. Local MicroRNA modulation using a novel anti-mir‑21‑eluting stent effectively prevents experimental in-stent restenosis. Arterioscler Thromb Vasc Biol. 2015;35(9):1945–53. https://doi.org/10.1161/ATVBAHA.115.305597Алиева А. М., Теплова Н. В., Резник Е. В., Байкова И. Е., Ахмедова М. Ф., Бутенко А. В. и др. Современные представления о роли микроРНК‑125 при сердечно-сосудистых заболеваниях: потенциальные биологические маркеры и терапевтические мишени. Российский медицинский журнал. 2023;29(4):311–324. https://doi.org/10.17816/medjrf112141.Alieva AM, Teplova NV, Reznik EV, Baikova IE, Akhmedova MF, Butenko AV, et al. Current insights into the role of miRNA‑125 in cardiovascular disease: potential biological markers and therapeutic targets. Russian Medicine. 2023;29(4):311–324. (In Russ.) https://doi.org/10.17816/medjrf112141Zhaolin Z, Jiaojiao C, Peng W, Yami L, Tingting Z, Jun T, et al. OxLDL induces vascular endothelial cell pyroptosis through miR‑125a‑5p/TET2 pathway. J Cell Physiol. 2019;234(5):7475–7491. https://doi.org/10.1002/jcp.27509Zhaolin Z, Jiaojiao C, Peng W, Yami L, Tingting Z, Jun T, et al. OxLDL induces vascular endothelial cell pyroptosis through miR‑125a‑5p/TET2 pathway. J Cell Physiol. 2019;234(5):7475–7491. https://doi.org/10.1002/jcp.27509Jaguszewski M, Osipova J, Ghadri JR, Napp LC, Widera C, Franke J, et al. A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction. Eur Heart J. 2014;35(15):999–1006. https://doi.org/10.1093/eurheartj/eht392Jaguszewski M, Osipova J, Ghadri JR, Napp LC, Widera C, Franke J, et al. A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction. Eur Heart J. 2014;35(15):999–1006. https://doi.org/10.1093/eurheartj/eht392Hueso M, Griñán R, Mallen A, Navarro E, Purqueras E,Gomá M, et al. MiR‑125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport. Biomed Pharmacother. 2022;146:112596. https://doi.org/10.1016/j.biopha.2021.112596Vigili de Kreutzenberg S, Giannella A, Ceolotto G. A miR‑125/Sirtuin‑7 pathway drives the pro-calcific potential of myeloid cells in diabetic vascular disease. Diabetologia. 2022;65(9): 1555–1568. https://doi.org/10.1007/s00125-022-05733-2Vigili de Kreutzenberg S, Giannella A, Ceolotto G. A miR‑125/Sirtuin‑7 pathway drives the pro-calcific potential of myeloid cells in diabetic vascular disease. Diabetologia. 2022;65(9): 1555–1568. https://doi.org/10.1007/s00125-022-05733-2Gager GM, Eyileten C, Postula M. association between the expression of MicroRNA‑125b and survival in patients with acute coronary syndrome and coronary multivessel disease. J. Front Cardiovasc Med. 2022;8(9):948006. https://doi.org/10.3389/fcvm.2022.948006Gager GM, Eyileten C, Postula M. association between the expression of MicroRNA‑125b and survival in patients with acute coronary syndrome and coronary multivessel disease. J. Front Cardiovasc Med. 2022;8(9):948006. https://doi.org/10.3389/fcvm.2022.948006Lv F, Liu L, Feng Q, Yang X. Long non-coding RNA MALAT1 and its target microRNA‑125b associate with disease risk, severity, and major adverse cardiovascular event of coronary heart disease. J Clin Lab Anal. 2021;35(4):e23593. https://doi.org/10.1002/jcla.23593Lv F, Liu L, Feng Q, Yang X. Long non-coding RNA MALAT1 and its target microRNA‑125b associate with disease risk, severity, and major adverse cardiovascular event of coronary heart disease. J Clin Lab Anal. 2021;35(4):e23593. https://doi.org/10.1002/jcla.23593Zhu Y, Zhu Y, Liu Y, Liu Y, Chen X. Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 correlates with microRNA‑125b/microRNA‑146a/microRNA‑203 and predicts 2‑year restenosis risk in coronary heart disease patients. Biomark Med. 2021;15(4):257–271. https://doi.org/10.2217/bmm‑2020-0715Zhu Y, Zhu Y, Liu Y, Liu Y, Chen X. Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 correlates with microRNA‑125b/microRNA‑146a/microRNA‑203 and predicts 2‑year restenosis risk in coronary heart disease patients. Biomark Med. 2021;15(4):257–271. https://doi.org/10.2217/bmm‑2020-0715Saadatian Z, Mansoori Y, Nariman-Saleh-Fam L, Daraei A, Vahed SZ, Navid S, et al. Peripheral blood mononuclear cells expression of miR‑200c, miR‑125b, miR‑27b, miR‑203, and miR‑155 in patients with significant or insignificant coronary artery stenosis. Sci Rep. 2023;13(1):18438. https://doi.org/10.1038/s41598-023-45146-8Saadatian Z, Mansoori Y, Nariman-Saleh-Fam L, Daraei A, Vahed SZ, Navid S, et al. Peripheral blood mononuclear cells expression of miR‑200c, miR‑125b, miR‑27b, miR‑203, and miR‑155 in patients with significant or insignificant coronary artery stenosis. Sci Rep. 2023;13(1):18438. https://doi.org/10.1038/s41598-023-45146-8Varga ZV, Zvara A, Faragó N, Kocsis GF, Pipicz M, Gáspár R, et al. MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs. Am J Physiol Heart Circ Physiol. 2014;307(2):216–227. https://doi.org/10.1152/ajpheart.00812.2013Varga ZV, Zvara A, Faragó N, Kocsis GF, Pipicz M, Gáspár R, et al. MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs. Am J Physiol Heart Circ Physiol. 2014;307(2):216–227. https://doi.org/10.1152/ajpheart.00812.2013Xiaochuan B, Qianfeng J, Min X, Xiao L. RASSF1 promotes cardiomyocyte apoptosis after acute myocardial infarction and is regulated by miR‑125b. J Cell Biochem. 2020;121(1):489–496. https://doi.org/10.1002/jcb.29236Xiaochuan B, Qianfeng J, Min X, Xiao L. RASSF1 promotes cardiomyocyte apoptosis after acute myocardial infarction and is regulated by miR‑125b. J Cell Biochem. 2020;121(1):489–496. https://doi.org/10.1002/jcb.29236Amin MMJ, Trevelyan CJ, Turner NA. MicroRNA‑214 in health and disease. Cells. 2021;10(12):3274. https://doi.org/10.3390/cells10123274Amin MMJ, Trevelyan CJ, Turner NA. MicroRNA‑214 in health and disease. Cells. 2021;10(12):3274. https://doi.org/10.3390/cells10123274Eguchi S, Takefuji M, Sakaguchi T, Ishihama S, Mori Y, Tsuda T, et al. Cardiomyocytes capture stem cell-derived, antiapoptotic microRNA‑214 via clathrin-mediated endocytosis in acute myocardial infarction. J Biol Chem. 2019;294(31):11665–11674. https://doi.org/10.1074/jbc.RA119.007537Eguchi S, Takefuji M, Sakaguchi T, Ishihama S, Mori Y, Tsuda T, et al. Cardiomyocytes capture stem cell-derived, antiapoptotic microRNA‑214 via clathrin-mediated endocytosis in acute myocardial infarction. J Biol Chem. 2019;294(31):11665–11674. https://doi.org/10.1074/jbc.RA119.007537Стабильная ишемическая болезнь сердца: Клинические рекомендации 2020 (04.09.2022). Утверждены Минздравом РФ. https://scardio.ru/content/Guidelines/2020/Clinic_rekom_IBSunlocked.pdfСтабильная ишемическая болезнь сердца: Клинические рекомендации 2020 (04.09.2022). Утверждены Минздравом РФ. https://scardio.ru/content/Guidelines/2020/Clinic_rekom_IBSunlocked.pdfStable Ischemic Heart Disease: Clinical Guidelines 2020 (04.09.2022). Approved by the Ministry of Health of the Russian Federation. (In Russ.) https://scardio.ru/content/Guidelines/2020/Clinic_rekom_IBS-unlocked.pdfStable Ischemic Heart Disease: Clinical Guidelines 2020 (04.09.2022). Approved by the Ministry of Health of the Russian Federation. (In Russ.) https://scardio.ru/content/Guidelines/2020/Clinic_rekom_IBS-unlocked.pdfVisseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al; ESC National Cardiac Societies; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34): 3227–3337. https://doi.org/10.1093/eurheartj/ehab484Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al; ESC National Cardiac Societies; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34): 3227–3337. https://doi.org/10.1093/eurheartj/ehab484

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