therapeuticЮжно-Российский журнал терапевтической практикиSouth Russian Journal of Therapeutic Practice2712-81563033-8344РостГМУ10.21886/2712-8156-2026-7-2-6-13therapeutic-720Research ArticleОБЗОРЫREVIEWSСовременный взгляд на генетический ландшафт дилатационной кардиомиопатии: от фундаментальных основ к персонализированной терапииDilated cardiomyopathy (DCM): a genetic landscape and clinical implicationshttps://orcid.org/0000-0003-2247-4242КузнецоваО. О.KuznetsovaO. O.

Кузнецова Оксана Олеговна, к.м.н., доцент кафедры кардиологии и функциональной диагностики ИПО; врач-кардиолог

Красноярск

Oksana O. Kuznetsova, Cand. Sci. (Med.), Associate Professor at the Department of Cardiology and Functional Diagnostics; cardiologist

Krasnoyarsk

isachenko102@inbox.ruhttps://orcid.org/0000-0002-6968-7627НикулинаС. Ю.NikulinaS. Yu.

Никулина Светлана Юрьевна, д.м.н., проф., заведующий кафедрой факультетской терапии

Красноярск

Svetlana Yu. Nikulina, Dr. Sci. (Med.), Professor of the Department of Faculty Therapy; Head of the Department of Faculty Therapy

Krasnoyarsk

nicoulina@mail.ruhttps://orcid.org/0000-0003-2977-1792ЧерноваА. А.ChernovaA. A.

Чернова Анна Александровна, д.м.н., профессор кафедры факультетской терапии; руководитель отдела науки и инноваций

Красноярск

Anna A. Chernova, Dr. Sci. (Med.), Professor, Head of Science and Innovation Department

Krasnoyarsk

anechkachernova@yandex.ruhttps://orcid.org/0000-0002-7165-4496МаксимовВ. Н.MaksimovV. N.

Максимов Владимир Николаевич, д.м.н., проф., заведующий лабораторией молекулярно-генетических исследований терапевтических заболеваний

Новосибирск

Vladimir N. Maksimov, Dr. Sci. (Med.), Professor, Head of the Laboratory of Molecular Genetic Research of Therapeutic Diseases

Novosibirsk

medik11@mail.ruФГБОУ ВО «Красноярский государственный медицинский университет им. проф. В. Ф. Войно-Ясенецкого» Минздрава России; ФГБУ «Федеральный центр сердечно-сосудистой хирургии» Минздрава РоссииРоссияV. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Federal Center for Cardiovascular SurgeryRussian FederationФГБОУ ВО «Красноярский государственный медицинский университет им. проф. В. Ф. Войно-Ясенецкого» Минздрава РоссииРоссияV. F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationФГБОУ ВО «Красноярский государственный медицинский университет им. проф. В. Ф. Войно-Ясенецкого» Минздрава России; Федеральный Сибирский научно-клинический центр ФМБА РоссииРоссияV. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Federal Siberian Scientific and Clinical Center of the FMBA of RussiaRussian FederationНаучно-исследовательский институт терапии и профилактической медицины СО РАМНРоссияResearch Institute of Therapy and Preventive Medicine of the Siberian Branch of the Russian Academy of Medical SciencesRussian Federation20262506202672613Copyright © Кузнецова О.О., Никулина С.Ю., Чернова А.А., Максимов В.Н., 20262026Кузнецова О.О., Никулина С.Ю., Чернова А.А., Максимов В.Н.Kuznetsova O.O., Nikulina S.Y., Chernova A.A., Maksimov V.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.therapeutic-j.ru/jour/article/view/720

Дилатационная кардиомиопатия (ДКМП) — этиологически гетерогенное заболевание миокарда с распространённостью до 1:250, ассоциированное с мутациями более чем в 100 генах, однако патогенные варианты идентифицируются лишь в 30–40% случаев. Настоящий обзор систематизирует современные данные о генетическом ландшафте ДКМП. Согласно международным критериям, лишь 12 генов (включая LMNA, TTN, MYH7, SCN5A, RBM20, DSP, FLNC) обладают высокой доказательной базой, тогда как большинство коммерческих панелей содержат гены с минимальным уровнем доказательств. Помимо моногенных форм, важную роль играют однонуклеотидные полиморфизмы в генах IL-32, CD247, MMP2, MBL2 и компонентах РААС, модулирующие риск развития заболевания через регуляцию воспаления и ремоделирования внеклеточного матрикса. Клиническая значимость генетического тестирования определяется возможностью стратификации риска внезапной сердечной смерти (особенно при мутациях в LMNA, RBM20, FLNC) и разработки персонализированных подходов к терапии. Таким образом, генетическое тестирование становится неотъемлемым инструментом современной кардиологии. Поиск литературных источников проводился в научных базах данных PubMed (https://pubmed.ncbi.nlm. nih.gov/), eLIBRARY.RU (https://elibrary.ru/), Embase (embase. com), Web of science (https://www.webofscience.com), Google Scholar (scholar.google.com) за период 2005–2025 гг.

Dilated cardiomyopathy (DCM) is an etiologically heterogeneous myocardial disease with a prevalence of up to 1:250 and is associated with mutations in more than 100 genes. However, pathogenic variants are identified in only 30–40% of cases. This review systematizes current data on the genetic landscape of DCM. According to international criteria, only 12 genes (including LMNA, TTN, MYH7, SCN5A, RBM20, DSP, FLNC) have a high level of evidence, whereas the majority of commercial gene panels include genes with minimal supporting data. In addition to monogenic forms, single nucleotide polymorphisms (SNPs) in genes such as IL-32, CD247, MMP2, MBL2, and components of the renin-angiotensin-aldosterone system (RAAS) play a significant role by modulating disease risk through the regulation of inflammation and extracellular matrix remodeling. The clinical significance of genetic testing lies in its ability to stratify the risk of sudden cardiac death (especially in the presence of mutations in LMNA, RBM20, FLNC) and to develop personalized therapeutic approaches. Thus, genetic testing is becoming an indispensable tool in modern cardiology. The search for literary sources was carried out in scientific databases PubMed (https://pubmed.ncbi.nlm. nih.gov/), eLIBRARY.RU (https://elibrary.ru/), Embase (embase.com), Web of science (https://www.webofscience.com), Google Scholar (scholar.google.com) for the period 2005–2025.

дилатационная кардиомиопатиягенетикастратификация рискаперсонализированная медицинаLMNATTNSCN5ARBM20dilated cardiomyopathygeneticsrisk stratificationpersonalized medicineLMNATTNSCN5ARBM20Исследование не имело спонсорской поддержки.ReferencesКучер А.Н., Слепцов А.А., Назаренко М.С. Генетический ландшафт дилатационной кардиомиопатии. Генетика. 2022;58(4):371-387.Kuchera A.N., Sleptcova A.A., Nazarenko M.S. Genetic Landscape of Dilated Cardiomyopathy. Russian Journal of Genetics. 2022;58(4):371-387. (In Russ.) DOI: 10.31857/S0016675822030080Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales-Villa R, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023;44(37):3503-3626. DOI: 10.1093/eurheartj/ehad194Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, BarrialesVilla R, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023;44(37):3503-3626. DOI: 10.1093/eurheartj/ehad194 3. Mazzarotto F, Tayal U, Buchan RJ, Midwinter W, Wilk A, Whiffin N, et al. Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy. Circulation. 2020;141(5):387-398. DOI: 10.1161/CIRCULATIONAHA.119.037661Mazzarotto F, Tayal U, Buchan RJ, Midwinter W, Wilk A, Whiffin N, et al. Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy. Circulation. 2020;141(5):387-398. DOI: 10.1161/CIRCULATIONAHA.119.037661Rubiś P. Charting the genetic landscape of dilated cardiomyopathy in Poland: first insights from a national perspective. Pol Arch Intern Med. 2025;135(9):17125. DOI: 10.20452/pamw.17125Rubiś P. Charting the genetic landscape of dilated cardiomyopathy in Poland: first insights from a national perspective. Pol Arch Intern Med. 2025;135(9):17125. DOI: 10.20452/pamw.17125Jordan E, Peterson L, Ai T, Asatryan B, Bronicki L, Brown E, et al. Evidence-Based Assessment of Genes in Dilated Cardiomyopathy. Circulation. 2021;144(1):7-19. DOI: 10.1161/CIRCULATIONAHA.120.053033Jordan E, Peterson L, Ai T, Asatryan B, Bronicki L, Brown E, et al. Evidence-Based Assessment of Genes in Dilated Cardiomyopathy. Circulation. 2021;144(1):7-19. DOI: 10.1161/CIRCULATIONAHA.120.053033McNally EM, Golbus JR, Puckelwartz MJ. Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest. 2013;123(1):19-26. DOI: 10.1172/JCI62862McNally EM, Golbus JR, Puckelwartz MJ. Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest. 2013;123(1):19-26. DOI: 10.1172/JCI62862Kim OH, Kim J, Kim Y, Lee S, Lee BH, Kim BJ, et al. Exploring novel MYH7 gene variants using in silico analysesin Korean patients with cardiomyopathy. BMC Med Genomics. 2024;17(1):225. DOI: 10.1186/s12920-024-02000-8Kim OH, Kim J, Kim Y, Lee S, Lee BH, Kim BJ, et al. Exploring novel MYH7 gene variants using in silico analysesin Korean patients with cardiomyopathy. BMC Med Genomics. 2024;17(1):225. DOI: 10.1186/s12920-024-02000-8Pettinato AM, Ladha FA, Mellert DJ, Legere N, Cohn R, Romano R, et al. Development of a Cardiac Sarcomere Functional Genomics Platform to Enable Scalable Interrogation of Human TNNT2 Variants. Circulation. 2020;142(23):2262-2275. DOI: 10.1161/CIRCULATIONAHA.120.047999Pettinato AM, Ladha FA, Mellert DJ, Legere N, Cohn R, Romano R, et al. Development of a Cardiac Sarcomere Functional Genomics Platform to Enable Scalable Interrogation of Human TNNT2 Variants. Circulation. 2020;142(23):2262-2275. DOI: 10.1161/CIRCULATIONAHA.120.047999Sedaghat-Hamedani F, Rebs S, El-Battrawy I, Chasan S, Krause T, Haas J, et al. Identification of SCN5a p.C335R Variant in a Large Family with Dilated Cardiomyopathy and Conduction Disease. Int J Mol Sci. 2021;22(23):12990. DOI: 10.3390/ijms222312990Sedaghat-Hamedani F, Rebs S, El-Battrawy I, Chasan S, Krause T, Haas J, et al. Identification of SCN5a p.C335R Variant in a Large Family with Dilated Cardiomyopathy and Conduction Disease. Int J Mol Sci. 2021;22(23):12990. DOI: 10.3390/ijms222312990Nishiyama T, Zhang Y, Cui M, Li H, Sanchez-Ortiz E, McAnally JR, et al. Precise genomic editing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy. Sci Transl Med. 2022;14(672):eade1633. DOI: 10.1126/scitranslmed.ade1633Nishiyama T, Zhang Y, Cui M, Li H, Sanchez-Ortiz E, McAnally JR, et al. Precise genomic editing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy. Sci Transl Med. 2022;14(672):eade1633. DOI: 10.1126/scitranslmed.ade1633Giri P, Jain D, Kumar A, Mohapatra B. Identification and in silico characterization of CSRP3 synonymous variantsin dilated cardiomyopathy. Mol Biol Rep. 2023;50(5):4105-4117. DOI: 10.1007/s11033-023-08314-7Giri P, Jain D, Kumar A, Mohapatra B. Identification and in silico characterization of CSRP3 synonymous variantsin dilated cardiomyopathy. Mol Biol Rep. 2023;50(5):4105-4117. DOI: 10.1007/s11033-023-08314-7JohnsonR,OtwayR,ChinE,HorvatC,OhanianM,Wilcox JAL, et al. DMD-AssociatedDilatedCardiomyopathy:Genotypes,Phenotypes, and Phenocopies. Circ Genom Precis Med. 2023;16(5):421-430. DOI: 10.1161/CIRCGEN.123.004221Johnson R, Otway R, Chin E, Horvat C, Ohanian M, Wilcox JAL, et al. DMD-Associated Dilated Cardiomyopathy: Genotypes, Phenotypes, and Phenocopies. Circ Genom Precis Med. 2023;16(5):421-430. DOI: 10.1161/CIRCGEN.123.004221Sivitskaya L, Danilenko N, Motuk I, Zhelev N. Splicing mutation in TAZ gene leading to exon skipping and Barth syndrome. Acta Myol. 2021;40(2):88-92. DOI: 10.36185/2532-1900-047Sivitskaya L, Danilenko N, Motuk I, Zhelev N. Splicing mutation in TAZ gene leading to exon skipping and Barth syndrome. Acta Myol. 2021;40(2):88-92. DOI: 10.36185/2532-1900-047Huang YS, Xing YL, Li HW. Heterozygous desmin gene (DES) mutation contributesto familial dilated cardiomyopathy. J Int Med Res. 2021;49(4):3000605211006598. DOI: 10.1177/03000605211006598Huang YS, Xing YL, Li HW. Heterozygous desmin gene (DES) mutation contributesto familial dilated cardiomyopathy. J Int Med Res. 2021;49(4):3000605211006598. DOI: 10.1177/03000605211006598Song XW, Su T, Li B, Huang YJ, He WX, Jiang LL, et al. Abnormal expression of PRKAG2-AS results in dysfunction of cardiomyocytes through regulating PRKAG2 transcription by interacting with PPARG. Clin Epigenetics. 2023;15(1):178. DOI: 10.1186/s13148-023-01591-wSong XW, Su T, Li B, Huang YJ, He WX, Jiang LL, et al. Abnormal expression of PRKAG2-AS results in dysfunction of cardiomyocytes through regulating PRKAG2 transcription by interacting with PPARG. Clin Epigenetics. 2023;15(1):178. DOI: 10.1186/s13148-023-01591-wTran DD, Lien NTK, Tung NV, Huu NC, Nguyen PT, Tien DA, et al. ThreeNovelPathogenicVariantsinUnrelatedVietnamesePatients with Cardiomyopathy. Diagnostics (Basel). 2024;14(23):2709. DOI: 10.3390/diagnostics14232709Tran DD, Lien NTK, Tung NV, Huu NC, Nguyen PT, Tien DA, et al. Three Novel Pathogenic Variants in Unrelated Vietnamese Patients with Cardiomyopathy. Diagnostics (Basel). 2024;14(23):2709. DOI: 10.3390/diagnostics14232709Mazzaccara C, Limongelli G, Petretta M, Vastarella R, Pacileo G, Bonaduce D, et al. A common polymorphism in the SCN5A gene is associated with dilated cardiomyopathy. J Cardiovasc Med (Hagerstown). 2018;19(7):344-350. DOI: 10.2459/JCM.0000000000000670Mazzaccara C, Limongelli G, Petretta M, Vastarella R, Pacileo G, Bonaduce D, et al. A common polymorphism in the SCN5A gene is associated with dilated cardiomyopathy. J Cardiovasc Med (Hagerstown). 2018;19(7):344-350. DOI: 10.2459/JCM.0000000000000670Peng Y, Zhong X, Wang Y, Zhou B, Song Y, Su M, et al. Genetic Association between Polymorphisms of Interleukin-32 and Dilated Cardiomyopathy in Chinese Han Population. Dis Markers. 2022;2022:5946290. DOI: 10.1155/2022/5946290Peng Y, Zhong X, Wang Y, Zhou B, Song Y, Su M, et al. Genetic Association between Polymorphisms of Interleukin-32 and Dilated Cardiomyopathy in Chinese Han Population. Dis Markers. 2022;2022:5946290. DOI: 10.1155/2022/5946290Li C, Xie X, Li K, Rao L. Polymorphisms of CD247 gene is associated with dilated cardiomyopathy in Chinese Han population. BMC Cardiovasc Disord. 2024;24(1):487. DOI: 10.1186/s12872-024-04160-yLi C, Xie X, Li K, Rao L. Polymorphisms of CD247 gene is associated with dilated cardiomyopathy in Chinese Han population. BMC Cardiovasc Disord. 2024;24(1):487. DOI: 10.1186/s12872-024-04160-yJia X, Meng L, Tang W, Sun L, Peng F, Zhang P. Impact ofthe gene polymorphismsintherenin-angiotensinsystemoncardiomyopathy risk: A meta-analysis. PLoS One. 2024;19(1):e0295626. DOI: 10.1371/journal.pone.0295626Jia X, Meng L, Tang W, Sun L, Peng F, Zhang P. Impact of the gene polymorphisms in the renin-angiotensin system on cardiomyopathy risk: A meta-analysis. PLoS One. 2024;19(1):e0295626. DOI: 10.1371/journal.pone.0295626Mao Y, Wei H, Gong Y, Peng L, Chen Y. Association of MBL2 gene polymorphisms and MBL levels with dilated cardiomyopathy in a Chinese Han population. BMC Med Genomics. 2024;17(1):11. DOI: 10.1186/s12920-023-01787-2Mao Y, Wei H, Gong Y, Peng L, Chen Y. Association of MBL2 gene polymorphisms and MBL levels with dilated cardiomyopathy in a Chinese Han population. BMC Med Genomics. 2024;17(1):11. DOI: 10.1186/s12920-023-01787-2Li S, Zeng X, Wang S, Xie X, Lan J. Association between MMP2 gene polymorphisms and dilated cardiomyopathy in a Chinese Han population. ESC Heart Fail. 2023;10(3):1793-1802. DOI: 10.1002/ehf2.14333Li S, Zeng X, Wang S, Xie X, Lan J. Association between MMP2 gene polymorphisms and dilated cardiomyopathy in a Chinese Han population. ESC Heart Fail. 2023;10(3):1793-1802. DOI: 10.1002/ehf2.14333Vaikhanskaya T.G., Sivitskaya L.N., Levdansky O.D., Kurushko T.V., Danilenko N.G. Genetic risk factorsfor dilated cardiomyopathy. Russian Journal of Cardiology. 2021;26(10):4628. (In Russ.) DOI: 10.15829/1560-4071-2021-4628Вайханская Т.Г., Сивицкая Л.Н., Левданский О.Д., Курушко Т.В., Даниленко Н.Г. Генетические факторы риска дилатационной кардиомиопатии. Российский кардиологический журнал. 2021;26(10):4628.Robles-Mezcua A, Rodríguez-Miranda L, Morcillo-Hidalgo L, Jiménez-Navarro M, García-Pinilla JM. Phenotype and progression among patients with dilated cardiomyopathy and RBM20 mutations. Eur J Med Genet. 2021;64(9):104278. DOI: 10.1016/j.ejmg.2021.104278Robles-Mezcua A, Rodríguez-Miranda L, Morcillo-Hidalgo L, Jiménez-Navarro M, García-Pinilla JM. Phenotype and progression among patients with dilated cardiomyopathy and RBM20 mutations. Eur J Med Genet. 2021;64(9):104278. DOI: 10.1016/j.ejmg.2021.104278Akinrinade O, Lesurf R; Genomics England Research Consortium; Lougheed J, Mondal T, Smythe J, et al. Age and Sex Differences in the Genetics of Cardiomyopathy. J Cardiovasc Transl Res. 2023;16(6):1287-1302. DOI: 10.1007/s12265-023-10411-8Akinrinade O, Lesurf R; Genomics England Research Consortium; Lougheed J, Mondal T, Smythe J, et al. Age and Sex Differences in the Genetics of Cardiomyopathy. J Cardiovasc Transl Res. 2023;16(6):1287-1302. DOI: 10.1007/s12265-023-10411-8Hovhannisyan Y, Li Z, Callon D, Suspène R, Batoumeni V, Canette A, et al. Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation. Stem Cell Res Ther. 2024;15(1):10. DOI: 10.1186/s13287-023-03619-7Hovhannisyan Y, Li Z, Callon D, Suspène R, Batoumeni V, Canette A, et al. Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation. Stem Cell Res Ther. 2024;15(1):10. DOI: 10.1186/s13287-023-03619-7Law ML, Cohen H, Martin AA, Angulski ABB, Metzger JM. Dysregulation of Calcium Handling in Duchenne Muscular Dystrophy-AssociatedDilated Cardiomyopathy: Mechanisms and Experimental Therapeutic Strategies.J Clin Med. 2020;9(2):520. DOI: 10.3390/jcm9020520Law ML, Cohen H, Martin AA, Angulski ABB, Metzger JM. Dysregulation of Calcium Handling in Duchenne Muscular Dystrophy-Associated-Dilated Cardiomyopathy: Mechanisms and Experimental Therapeutic Strategies.J Clin Med. 2020;9(2):520. DOI: 10.3390/jcm9020520Wei Y,CaoH,Peng YY, ZhangB.Alteratedgene expressionindilated cardiomyopathy after left ventricular assist device support by bioinformatics analysis. Front Cardiovasc Med. 2023;10:1013057. DOI: 10.3389/fcvm.2023.1013057Wei Y, Cao H, Peng YY, Zhang B. Alterated gene expression in dilated cardiomyopathy after left ventricular assist device support by bioinformatics analysis. Front Cardiovasc Med. 2023;10:1013057. DOI: 10.3389/fcvm.2023.1013057Newman NA, Burke MA. Dilated Cardiomyopathy: A Genetic Journey from Past to Future. Int J Mol Sci. 2024;25(21):11460. DOI: 10.3390/ijms252111460Newman NA, Burke MA. Dilated Cardiomyopathy: A Genetic Journey from Past to Future. Int J Mol Sci. 2024;25(21):11460. DOI: 10.3390/ijms252111460Newman NA, Burke MA. Dilated Cardiomyopathy: A Genetic Journey from Past to Future. Int J Mol Sci. 2024;25(21):11460. DOI: 10.3390/ijms252111460

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