medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.06.20-28medgen-2486Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHРедкие генетические варианты SYNPO2L при раннем инфаркте миокардаSYNPO2L  gene rare variants in the development of early myocardial infarctionМирошниковаВ. В.MiroshnikovaV. V.

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

6/8, Lev Tolstoy st., Saint-Petersburg, 197022

ДрачеваК. В.DrachevaK. V.

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

628412, г. Сургут, пр-т Ленина, д. 1

6/8, Lev Tolstoy st., Saint-Petersburg, 197022

1, Lenin Avenue, Surgut, 628412

ДаниловЛ. Г.DanilovL. G.

628412, г. Сургут, пр-т Ленина, д. 1

199034, г. Санкт-Петербург, Университетская набережная, д. 7/9

1, Lenin Avenue, Surgut, 628412

7/9, Universitetskaya naberezhnaya, Saint-Petersburg, 199034

ДонниковМ. Ю.DonnikovM. Yu.

628412, г. Сургут, пр-т Ленина, д. 1

1, Lenin Avenue, Surgut, 628412

ВоробьевА. С.VorobevA. S.

628412, г. Сургут, пр-т Ленина, д. 1

1, Lenin Avenue, Surgut, 628412

МорозкинаА. В.MorozkinaA. V.

628412, г. Сургут, пр-т Ленина, д. 1

1, Lenin Avenue, Surgut, 628412

ИзюмченкоА. Д.IzumchenkoA. D.

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

6/8, Lev Tolstoy st., Saint-Petersburg, 197022

КусакинА. В.KusakinA. V.

628412, г. Сургут, пр-т Ленина, д. 1

197022, г. Санкт-Петербург, ул. Профессора Попова, д. 9

1, Lenin Avenue, Surgut, 628412

9, Prof. Popova st., Saint Petersburg, 197022

ЭйсмонтЮ. А.EismontYu. А.

197022, г. Санкт-Петербург, ул. Профессора Попова, д. 9

199106, г. Санкт-Петербург, пр-т Большой В.о., д. 90, к. 2

9, Prof. Popova st., Saint Petersburg, 197022

90-2 Bolshoy prospekt, Saint-Petersburg, 199106, St. Petersburg

КоваленкоЛ. В.KovalenkoL. V.

628412, г. Сургут, пр-т Ленина, д. 1

1, Lenin Avenue, Surgut, 628412

УрванцеваИ. А.UrvantsevaI. A.

628412, г. Сургут, пр-т Ленина, д. 1

628400, г. Сургут, пр-т Ленина, д. 69/1

1, Lenin Avenue, Surgut, 628412

69/1, Lenin Avenue, Surgut, 628400

ГлотовО. С.GlotovO. S.

197022, г. Санкт-Петербург, ул. Профессора Попова, д. 9

199034, г. Санкт-Петербург, Менделеевская линия, д. 3

9, Prof. Popova st., Saint Petersburg, 197022

3, Mendeleevskaya line, Saint Petersburg, 199034

ПчелинаС. Н.PchelinaS. N.

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

6/8, Lev Tolstoy st., Saint-Petersburg, 197022

Первый Санкт-Петербургский Государственный Медицинский Университет им. акад. И.П. ПавловаРоссияPavlov First Saint-Petersburg State Medical UniversityRussian FederationПервый Санкт-Петербургский Государственный Медицинский Университет им. акад. И.П. Павлова; БУ ВО ХМАО-Югры Сургутский государственный университетРоссияPavlov First Saint-Petersburg State Medical University; Surgut State UniversityRussian FederationБУ ВО ХМАО-Югры Сургутский государственный университет; Санкт-Петербургский Государственный УниверситетРоссияSurgut State University; Saint-Petersburg State UniversityRussian FederationБУ ВО ХМАО-Югры Сургутский государственный университетРоссияSurgut State UniversityRussian FederationБУ ВО ХМАО-Югры Сургутский государственный университет; Детский научно-клинический центр инфекционных болезней Федерального медико-биологического агентстваРоссияSurgut State University; Children’s Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological AgencyRussian FederationДетский научно-клинический центр инфекционных болезней Федерального медико-биологического агентства; ООО СербалабРоссияChildren’s Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency; «Cerbalab» LtdRussian FederationБУ ВО ХМАО-Югры Сургутский государственный университет; БУ ХМАО-Югры Окружной кардиологический диспансер «Центр диагностики и сердечно-сосудистой хирургии»РоссияSurgut State University; The Khanty-Mansi Autonomous Okrug – Yugra Diagnostics and Cardiovascular Surgery Center (cardiology clinic)Russian FederationДетский научно-клинический центр инфекционных болезней Федерального медико-биологического агентства; Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. ОттаРоссияChildren’s Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency; Research Institute of Obstetrics and Gynecology named after D.O. OttRussian Federation2024210820242362028Copyright © Мирошникова В.В., Драчева К.В., Данилов Л.Г., Донников М.Ю., Воробьев А.С., Морозкина А.В., Изюмченко А.Д., Кусакин А.В., Эйсмонт Ю.А., Коваленко Л.В., Урванцева И.А., Глотов О.С., Пчелина С.Н., 20242024Мирошникова В.В., Драчева К.В., Данилов Л.Г., Донников М.Ю., Воробьев А.С., Морозкина А.В., Изюмченко А.Д., Кусакин А.В., Эйсмонт Ю.А., Коваленко Л.В., Урванцева И.А., Глотов О.С., Пчелина С.Н.Miroshnikova V.V., Dracheva K.V., Danilov L.G., Donnikov M.Y., Vorobev A.S., Morozkina A.V., Izumchenko A.D., Kusakin A.V., Eismont Y.А., Kovalenko L.V., Urvantseva I.A., Glotov O.S., Pchelina S.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.medgen-journal.ru/jour/article/view/2486

Инфаркт миокарда (ИМ) является одной из самых распространенных причин смерти и инвалидизации взрослого населения. В настоящее время наблюдается рост заболеваемости ИМ в молодом возрасте. Независимым фактором риска ИМ в молодом возрасте является наследственная предрасположенность. В данной работе был проведен поиск редких генетических вариантов, связанных с развитием сердечно-сосудистых заболеваний, путём полноэкзомного секвенирования у 8 пациентов, перенесших ИМ до 45 лет, у которых на предыдущем этапе были исключены основные генетические факторы риска ИМ − моногенные дислипидемии и тромбофилия. У двух пациентов были выявлены патогенные варианты гена SYNPO2L: p.(Arg630Leu) (rs143723429) и не описанный ранее вариант p.(Arg910Gln). Полученные данные дают основание предполагать вовлеченность гена SYNPO2L, кодирующего белок сократительной мышечной функции, в патогенез раннего ИМ.

Myocardial infarction (MI), being the main complication of coronary heart disease (CHD), is one of the most common causes of death and disability in the adult population. Currently, there is an increase in the incidence of MI at a young age. An independent risk factor for MI at a young age is hereditary predisposition. In this work, we searched for rare genetic variants associated with the development of cardiovascular diseases using whole-exome sequencing in patients who had suffered an MI before the age of 45 years, and for whom the main genetic risk factors for MI − monogenic dyslipidemias and thrombophilia – were excluded. In two patients, rare variants of the SYNPO2L gene were identified − p.(Arg630Leu) (rs143723429) and a previously undescribed variant p.(Arg910Gln), leading to amino acid substitutions that can lead to dysfunction of the corresponding protein. The data obtained suggest the involvement of the SYNPO2L gene, encoding a protein of contractile muscle function, in the pathogenesis of early MI.

инфаркт миокардаполноэкзомное секвенированиеSYNPO2LMyocardial infarctionwhole exome sequencingSYNPO2LThe study was carried out with financial support from the Ugra Scientific and Technological Development Foundation under scientific project No. 2023-126-05.ReferencesШальнова С.А., Драпкина О.М., Куценко В.А. и др. Инфаркт миокарда в популяции некоторых регионов России и его прогностическое значение. Российский кардиологический журнал. 2022;27(6):4952. doi:10.15829/15604071-2022-4952. EDN OCPROJШальнова С.А., Драпкина О.М., Куценко В.А. и др. Инфаркт миокарда в популяции некоторых регионов России и его прогностическое значение. Российский кардиологический журнал. 2022;27(6):4952. doi:10.15829/15604071-2022-4952. EDN OCPROJDai X., Wiernek S., Evans J. P., Runge, M. S. Genetics of coronary artery disease and myocardial infarction. World journal of cardiology. 2016;8(1),1-23. doi: 10.4330/wjc.v8.i1.1Dai X., Wiernek S., Evans J. P., Runge, M. S. Genetics of coronary artery disease and myocardial infarction. World journal of cardiology. 2016;8(1),1-23. doi: 10.4330/wjc.v8.i1.1Holmen O.L., Zhang H., Zhou W., et al. No large-effect low-frequency coding variation found for myocardial infarction. Human molecular genetics. 2014;23(17), 4721-4728. doi: 10.1093/hmg/ddu175Holmen O.L., Zhang H., Zhou W., et al. No large-effect low-frequency coding variation found for myocardial infarction. Human molecular genetics. 2014;23(17), 4721-4728. doi: 10.1093/hmg/ddu175The CARDIoGRAMplusC4D Consortium., Deloukas, P., Kanoni, S. et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013;45(1), 25–33. https://doi.org/10.1038/ng.2480The CARDIoGRAMplusC4D Consortium., Deloukas, P., Kanoni, S. et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013;45(1), 25–33. https://doi.org/10.1038/ng.2480Do R., Stitziel N., Won H.H. et al. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature. 2015;518(7537), 102–106. https://doi.org/10.1038/nature13917Do R., Stitziel N., Won H.H. et al. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature. 2015;518(7537), 102–106. https://doi.org/10.1038/nature13917Jeon Y., Jeon S., Choi W.H., et al. Genome-wide analyses of earlyonset acute myocardial infarction identify 29 novel loci by whole genome sequencing. Human Genetics. 2023;142(2), 231-243. https://doi.org/10.1007/s00439-022-02495-0Jeon Y., Jeon S., Choi W.H., et al. Genome-wide analyses of earlyonset acute myocardial infarction identify 29 novel loci by whole genome sequencing. Human Genetics. 2023;142(2), 231-243. https://doi.org/10.1007/s00439-022-02495-0Badescu M.C., Butnariu L.I., Costache A.D., et al. Acute Myocardial Infarction in Patients with Hereditary Thrombophilia—A Focus on Factor V Leiden and Prothrombin G20210A. Life. 2023;13(6), 1371. doi: 10.3390/life13061371Badescu M.C., Butnariu L.I., Costache A.D., et al. Acute Myocardial Infarction in Patients with Hereditary Thrombophilia—A Focus on Factor V Leiden and Prothrombin G20210A. Life. 2023;13(6), 1371. doi: 10.3390/life13061371Отева Э.А., Николаева А.А., Масленников А.Б. и др. Особенности липидно-гормональных взаимосвязей у молодых мужчин, перенесших инфаркт миокарда (по материалам семейных регистров в Новосибирске и Бишкеке). Терапевтический архив. 1994;66(9), 38-41.Отева Э.А., Николаева А.А., Масленников А.Б. и др. Особенности липидно-гормональных взаимосвязей у молодых мужчин, перенесших инфаркт миокарда (по материалам семейных регистров в Новосибирске и Бишкеке). Терапевтический архив. 1994;66(9), 38-41.Brænne I., Reiz B., Medack A. et al. Whole-exome sequencing in an extended family with myocardial infarction unmasks familial hypercholesterolemia. BMC Cardiovasc Disord. 2014;14, 108. https://doi. org/10.1186/1471-2261-14-108Brænne I., Reiz B., Medack A. et al. Whole-exome sequencing in an extended family with myocardial infarction unmasks familial hypercholesterolemia. BMC Cardiovasc Disord. 2014;14, 108. https://doi. org/10.1186/1471-2261-14-108Lee C., Cui Y., Song J., et al. Effects of familial hypercholesterolemia-associated genes on the phenotype of premature myocardial infarction. Lipids Health Dis. 2019;18;1-8, 95. https://doi.org/10.1186/ s12944-019-1042-3Lee C., Cui Y., Song J., et al. Effects of familial hypercholesterolemia-associated genes on the phenotype of premature myocardial infarction. Lipids Health Dis. 2019;18;1-8, 95. https://doi.org/10.1186/ s12944-019-1042-3Khattab M.N., Abbas A., Alhalabi N., Nouh G. Myocardial Infarction with ST Segment Elevation in 19-Year-Old Adult with Multiple Genetic Mutations: A Case Report. 2023;5(1):1044.Khattab M.N., Abbas A., Alhalabi N., Nouh G. Myocardial Infarction with ST Segment Elevation in 19-Year-Old Adult with Multiple Genetic Mutations: A Case Report. 2023;5(1):1044.Cui Y., Li S., Zhang F., et al. Prevalence of familial hypercholesterolemia in patients with premature myocardial infarction. Clinical Cardiology, 2019;42(3), 385-390. https://doi.org/10.1002/clc.23154Cui Y., Li S., Zhang F., et al. Prevalence of familial hypercholesterolemia in patients with premature myocardial infarction. Clinical Cardiology, 2019;42(3), 385-390. https://doi.org/10.1002/clc.23154Brænne I., Kleinecke M., Reiz B. et al. Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction. Eur J Hum Genet. 2016;24(2),191–197. https://doi.org/10.1038/ejhg.2015.100Brænne I., Kleinecke M., Reiz B. et al. Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction. Eur J Hum Genet. 2016;24(2),191–197. https://doi.org/10.1038/ejhg.2015.100Khera A.V., Chaffin M., Zekavat S.M., et al. Whole-genome sequencing to characterize monogenic and polygenic contributions in patients hospitalized with early-onset myocardial infarction. Circulation 2019;139(13),1593-1602. https://doi.org/10.1161/CIRCULATIONAHA.118.035658Khera A.V., Chaffin M., Zekavat S.M., et al. Whole-genome sequencing to characterize monogenic and polygenic contributions in patients hospitalized with early-onset myocardial infarction. Circulation 2019;139(13),1593-1602. https://doi.org/10.1161/CIRCULATIONAHA.118.035658Ghorbani M.J., Razmi N., Tabei S.M. et al. A substitution mutation in LRP8 gene is significantly associated with susceptibility to familial myocardial infarction. ARYA atherosclerosis. 2020;16(6), 301. https://doi.org/10.22122/arya.v16i6.1797Ghorbani M.J., Razmi N., Tabei S.M. et al. A substitution mutation in LRP8 gene is significantly associated with susceptibility to familial myocardial infarction. ARYA atherosclerosis. 2020;16(6), 301. https://doi.org/10.22122/arya.v16i6.1797Shen G.Q., Girelli D., Li L., et al. A novel molecular diagnostic marker for familial and early-onset coronary artery disease and myocardial infarction in the LRP8 gene. Circ Cardiovasc Genet 2014;7(4):514-20 https://doi.org/10.1161/CIRCGENETICS.113.000321Shen G.Q., Girelli D., Li L., et al. A novel molecular diagnostic marker for familial and early-onset coronary artery disease and myocardial infarction in the LRP8 gene. Circ Cardiovasc Genet 2014;7(4):514-20 https://doi.org/10.1161/CIRCGENETICS.113.000321Lee J.Y., Moon S., Kim Y.K., et al. Genome-based exome sequencing analysis identifies GYG1, DIS3L and DDRGK1 are associated with myocardial infarction in Koreans. Journal of Genetics. 2017;96(6), 1041–1046. doi:10.1007/s12041-017-0854-zLee J.Y., Moon S., Kim Y.K., et al. Genome-based exome sequencing analysis identifies GYG1, DIS3L and DDRGK1 are associated with myocardial infarction in Koreans. Journal of Genetics. 2017;96(6), 1041–1046. doi:10.1007/s12041-017-0854-zМирошникова В.В., Пчелина С.Н., Донников М.Ю. и др. Генетическое тестирование в кардиологии с помощью NGS панели: от оценки риска заболевания до фармакогенетики. Фармакогенетика и фармакогеномика. 2023;(1):7–19. https://doi. org/10.37489/2588-0527-2023-1-7-19Мирошникова В.В., Пчелина С.Н., Донников М.Ю. и др. Генетическое тестирование в кардиологии с помощью NGS панели: от оценки риска заболевания до фармакогенетики. Фармакогенетика и фармакогеномика. 2023;(1):7–19. https://doi. org/10.37489/2588-0527-2023-1-7-19Bolger A.M., Lohse M., Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics (Oxford, England). 2014;30(15), 2114–2120. https://doi.org/10.1093/bioinformatics/ btu170Bolger A.M., Lohse M., Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics (Oxford, England). 2014;30(15), 2114–2120. https://doi.org/10.1093/bioinformatics/ btu170Li H., Durbin R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics. 2009; 25(14), 1754–1760 https://doi.org/10.1093/bioinformatics/btp324Li H., Durbin R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics. 2009; 25(14), 1754–1760 https://doi.org/10.1093/bioinformatics/btp324Poplin R., Chang P.C., Alexander D., et al. A universal SNP and small-indel variant caller using deep neural networks. Nature Biotechnology. 2018;36(10),983–987. doi: https://doi.org/10.1038/ nbt.4235Poplin R., Chang P.C., Alexander D., et al. A universal SNP and small-indel variant caller using deep neural networks. Nature Biotechnology. 2018;36(10),983–987. doi: https://doi.org/10.1038/ nbt.4235McLaren W., Gil L., Hunt S.E., et al. The Ensembl Variant Effect Predictor. Genome Biology. 2016;17(1):122. doi:10.1186/s13059-016-0974-4McLaren W., Gil L., Hunt S.E., et al. The Ensembl Variant Effect Predictor. Genome Biology. 2016;17(1):122. doi:10.1186/s13059-016-0974-4Barbitoff Y.A., Khmelkova D.N., Pomerantseva E.A., et al. Expanding the Russian allele frequency reference via cross-laboratory data integration: insights from 6,096 exome samples. MedRXiv, 2021;2021-11. doi: https://doi.org/10.1101/2021.11.02.21265801Barbitoff Y.A., Khmelkova D.N., Pomerantseva E.A., et al. Expanding the Russian allele frequency reference via cross-laboratory data integration: insights from 6,096 exome samples. MedRXiv, 2021;2021-11. doi: https://doi.org/10.1101/2021.11.02.21265801Van Eldik W., Beqqali A., Monshouwer-Kloots J., Mummery C., Passier, R. Cytoskeletal heart-enriched actin-associated protein (CHAP) is expressed in striated and smooth muscle cells in chick and mouse during embryonic and adult stages. International Journal of Developmental Biology/ 2011;55(6). DOI: 10.1387/ ijdb.103207wvVan Eldik W., Beqqali A., Monshouwer-Kloots J., Mummery C., Passier, R. Cytoskeletal heart-enriched actin-associated protein (CHAP) is expressed in striated and smooth muscle cells in chick and mouse during embryonic and adult stages. International Journal of Developmental Biology/ 2011;55(6). DOI: 10.1387/ ijdb.103207wvBeqqali A., Monshouwer-Kloots J., Monteiro R., et al. CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function. J Cell Sci. 2010;123:1141–50. doi: 10.1242/jcs.063859Beqqali A., Monshouwer-Kloots J., Monteiro R., et al. CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function. J Cell Sci. 2010;123:1141–50. doi: 10.1242/jcs.063859Van Eldik W., Den Adel B., Monshouwer-Kloots J., et al. Z-disc protein CHAPb induces cardiomyopathy and contractile dysfunction in the postnatal heart. PLoS One. 2017;12(12), e0189139. https:// doi.org/10.1371/journal.pone.0189139Van Eldik W., Den Adel B., Monshouwer-Kloots J., et al. Z-disc protein CHAPb induces cardiomyopathy and contractile dysfunction in the postnatal heart. PLoS One. 2017;12(12), e0189139. https:// doi.org/10.1371/journal.pone.0189139Lohanadan K., Molt S., Dierck F., et al. Isoform-specific functions of synaptopodin-2 variants in cytoskeleton stabilization and autophagy regulation in muscle under mechanical stress. Experimental Cell Research. 2021;408(2), 112865. https://doi. org/10.1016/j.yexcr.2021.112865Lohanadan K., Molt S., Dierck F., et al. Isoform-specific functions of synaptopodin-2 variants in cytoskeleton stabilization and autophagy regulation in muscle under mechanical stress. Experimental Cell Research. 2021;408(2), 112865. https://doi. org/10.1016/j.yexcr.2021.112865Williams Z.J., Velez-Irizarry D., Gardner K., Valberg S. J. Integrated proteomic and transcriptomic profiling identifies aberrant gene and protein expression in the sarcomere, mitochondrial complex I, and the extracellular matrix in Warmblood horses with myofibrillar myopathy. BMC genomics. 2021;22, 1-20. https://doi.org/10.1186/s12864-021-07758-0Williams Z.J., Velez-Irizarry D., Gardner K., Valberg S. J. Integrated proteomic and transcriptomic profiling identifies aberrant gene and protein expression in the sarcomere, mitochondrial complex I, and the extracellular matrix in Warmblood horses with myofibrillar myopathy. BMC genomics. 2021;22, 1-20. https://doi.org/10.1186/s12864-021-07758-0Banerjee A., Dashtban A., Chen S., et al. Identifying subtypes of heart failure from three electronic health record sources with machine learning: an external, prognostic, and genetic validation study. The Lancet Digital Health. 2023;5(6), e370-e379. DOI: https://doi. org/10.1016/S2589-7500(23)00065-1Banerjee A., Dashtban A., Chen S., et al. Identifying subtypes of heart failure from three electronic health record sources with machine learning: an external, prognostic, and genetic validation study. The Lancet Digital Health. 2023;5(6), e370-e379. DOI: https://doi. org/10.1016/S2589-7500(23)00065-1Nielsen J.B., Fritsche L.G., Zhou W., et al. Genome-wide study of atrial fibrillation identifies seven risk loci and highlights biological pathways and regulatory elements involved in cardiac development. The American Journal of Human Genetics. 2018;102(1), 103-115. https://doi.org/10.1016/j.ajhg.2017.12.003Nielsen J.B., Fritsche L.G., Zhou W., et al. Genome-wide study of atrial fibrillation identifies seven risk loci and highlights biological pathways and regulatory elements involved in cardiac development. The American Journal of Human Genetics. 2018;102(1), 103-115. https://doi.org/10.1016/j.ajhg.2017.12.003Roberts J.D., Hu D., Heckbert S.R., et al. Genetic investigation into the differential risk of atrial fibrillation among black and white individuals. JAMA cardiology. 2016;1(4), 442-450. doi:10.1001/ jamacardio.2016.1185Roberts J.D., Hu D., Heckbert S.R., et al. Genetic investigation into the differential risk of atrial fibrillation among black and white individuals. JAMA cardiology. 2016;1(4), 442-450. doi:10.1001/ jamacardio.2016.1185Ellinor P.T, Lunetta K.L, Albert C.M., et al. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet. 2012;44(6): 670–675. https://doi.org/10.1038/ng.2261Ellinor P.T, Lunetta K.L, Albert C.M., et al. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet. 2012;44(6): 670–675. https://doi.org/10.1038/ng.2261Christophersen I.E., Rienstra M., Roselli C., et al. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nat. Genet. 2017;49(6), 946–952 (2017). https://doi.org/10.1038/ng.3843Christophersen I.E., Rienstra M., Roselli C., et al. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nat. Genet. 2017;49(6), 946–952 (2017). https://doi.org/10.1038/ng.3843Hsu J., Gore-Panter S., Tchou G., et al.. Genetic control of left atrial gene expression yields insights into the genetic susceptibility for atrial fibrillation. Circulation: Genomic and Precision Medicine. 2018;11(3), e002107. https://doi.org/10.1161/CIRCGEN.118.002107Hsu J., Gore-Panter S., Tchou G., et al.. Genetic control of left atrial gene expression yields insights into the genetic susceptibility for atrial fibrillation. Circulation: Genomic and Precision Medicine. 2018;11(3), e002107. https://doi.org/10.1161/CIRCGEN.118.002107Roselli C., Chaffin M.D., Weng L.C., et al.. Multi-ethnic genomewide association study for atrial fibrillation. Nature Genetics. 2018;50(9),1225-1233. https://doi.org/10.1038/s41588-018-0133-9Roselli C., Chaffin M.D., Weng L.C., et al.. Multi-ethnic genomewide association study for atrial fibrillation. Nature Genetics. 2018;50(9),1225-1233. https://doi.org/10.1038/s41588-018-0133-9Lin H., Yin X., Xie Z., et al. Methylome-wide Association Study of Atrial Fibrillation in Framingham Heart Study. Scientific Reports. 2017;7 (1):40377. doi:10.1038/srep40377. http://dx.doi.org/10.1038/srep40377.Lin H., Yin X., Xie Z., et al. Methylome-wide Association Study of Atrial Fibrillation in Framingham Heart Study. Scientific Reports. 2017;7 (1):40377. doi:10.1038/srep40377. http://dx.doi.org/10.1038/srep40377.Patel K.K., Venkatesan C., Abdelhalim H. et al. Genomic approaches to identify and investigate genes associated with atrial fibrillation and heart failure susceptibility. Hum Genomics; 2023;17,47. https://doi. org/10.1186/s40246-023-00498-0Patel K.K., Venkatesan C., Abdelhalim H. et al. Genomic approaches to identify and investigate genes associated with atrial fibrillation and heart failure susceptibility. Hum Genomics; 2023;17,47. https://doi. org/10.1186/s40246-023-00498-0Shah S., Henry A., Roselli C., et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure Nature Communications. 2020;11(1), 163. https://doi.org/10.1038/s41467-019-13690-5Shah S., Henry A., Roselli C., et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure Nature Communications. 2020;11(1), 163. https://doi.org/10.1038/s41467-019-13690-5Shishkova K.Y., Nikulina S.Y., Shulman V.A., et al. The role of single-nucleotide polymorphism rs10824026 of the SYNPO2L gene in the development of atrial fibrillation in a study in the East-Siberian population. CardioSomatics. 2019;10(4).34-38. DOI:10.26442/222 17185.2019.4.190722Shishkova K.Y., Nikulina S.Y., Shulman V.A., et al. The role of single-nucleotide polymorphism rs10824026 of the SYNPO2L gene in the development of atrial fibrillation in a study in the East-Siberian population. CardioSomatics. 2019;10(4).34-38. DOI:10.26442/222 17185.2019.4.190722Thériault S., Imboden M., Biggs M. L., et al. Genome-wide analyses identify SCN5A as a susceptibility locus for premature atrial contraction frequency. Iscience. 2022;25(10). https://doi. org/10.1016/j.isci.2022.105210Thériault S., Imboden M., Biggs M. L., et al. Genome-wide analyses identify SCN5A as a susceptibility locus for premature atrial contraction frequency. Iscience. 2022;25(10). https://doi. org/10.1016/j.isci.2022.105210Lubitz S.A, Brody J.A, Bihlmeyer N.A, et al. Whole Exome Sequencing in Atrial Fibrillation. PLo S genetics. 2016;12(9):e1006284. https://doi.org/10.1371/journal.pgen.1006284Lubitz S.A, Brody J.A, Bihlmeyer N.A, et al. Whole Exome Sequencing in Atrial Fibrillation. PLo S genetics. 2016;12(9):e1006284. https://doi.org/10.1371/journal.pgen.1006284Schmidt A.F., Bourfiss M., Alasiri A., et al. Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity. Science advances. 2023;9(17), eadd4984. doi: 10.1126/sciadv.add4984Schmidt A.F., Bourfiss M., Alasiri A., et al. Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity. Science advances. 2023;9(17), eadd4984. doi: 10.1126/sciadv.add4984Ning C., Fan L., Jin M. et al. Genome-wide association analysis of left ventricular imaging-derived phenotypes identifies 72 risk loci and yields genetic insights into hypertrophic cardiomyopathy. Nat Commun. 2023;14,7900. https://doi.org/10.1038/s41467-023-43771-5Ning C., Fan L., Jin M. et al. Genome-wide association analysis of left ventricular imaging-derived phenotypes identifies 72 risk loci and yields genetic insights into hypertrophic cardiomyopathy. Nat Commun. 2023;14,7900. https://doi.org/10.1038/s41467-023-43771-5Brugada R., Tapscott T., Czernuszewicz G.Z., et al. Identification of a genetic locus for familial atrial fibrillation. N Engl J Med. 1997;336(13):905–911. DOI: 10.1056/NEJM199703273361302Brugada R., Tapscott T., Czernuszewicz G.Z., et al. Identification of a genetic locus for familial atrial fibrillation. N Engl J Med. 1997;336(13):905–911. DOI: 10.1056/NEJM199703273361302Clausen A.G., Vad O.B., Andersen J.H., Olesen M.S. Loss-offunction variants in the SYNPO2L gene are associated with atrial fibrillation. Frontiers in cardiovascular medicine. 2021;8, 650667. https://doi.org/10.3389/fcvm.2021.650667Clausen A.G., Vad O.B., Andersen J.H., Olesen M.S. Loss-offunction variants in the SYNPO2L gene are associated with atrial fibrillation. Frontiers in cardiovascular medicine. 2021;8, 650667. https://doi.org/10.3389/fcvm.2021.650667Ruddox V., Sandven I., Munkhaugen J.,. et al. Atrial fibrillation and the risk for myocardial infarction, all-cause mortality and heart failure: a systematic review and meta-analysis. European journal of preventive cardiology. 2017;24(14),1555-1566. https://doi. org/10.1177/204748731771576Ruddox V., Sandven I., Munkhaugen J.,. et al. Atrial fibrillation and the risk for myocardial infarction, all-cause mortality and heart failure: a systematic review and meta-analysis. European journal of preventive cardiology. 2017;24(14),1555-1566. https://doi. org/10.1177/204748731771576Mishra A., Malik R., Hachiya T. et al. Stroke genetics informs drug discovery and risk prediction across ancestries. Nature. 2022;611(7934), 115-123. https://doi.org/10.1038/s41586-022-05165-3Mishra A., Malik R., Hachiya T. et al. Stroke genetics informs drug discovery and risk prediction across ancestries. Nature. 2022;611(7934), 115-123. https://doi.org/10.1038/s41586-022-05165-3Kraja A.T., Cook J.P., Warren H.R., et al. New blood pressure– associated loci identified in meta-analyses of 475 000 individuals. Circulation: Cardiovascular Genetics. 2017;10(5), e001778. DOI: 10.1161/CIRCGENETICS.117.001778Kraja A.T., Cook J.P., Warren H.R., et al. New blood pressure– associated loci identified in meta-analyses of 475 000 individuals. Circulation: Cardiovascular Genetics. 2017;10(5), e001778. DOI: 10.1161/CIRCGENETICS.117.001778Wang F., Liu Y., Liao H., et al. Genetic variants on SCN5A, KCNQ1, and KCNH2 in patients with ventricular arrhythmias during acute myocardial infarction in a Chinese population. Cardiology. 2020;145(1), 38-45. https://doi.org/10.1159/000502833Wang F., Liu Y., Liao H., et al. Genetic variants on SCN5A, KCNQ1, and KCNH2 in patients with ventricular arrhythmias during acute myocardial infarction in a Chinese population. Cardiology. 2020;145(1), 38-45. https://doi.org/10.1159/000502833Olszak-Waśkiewicz M., Dziuk M., Kubik L., Kaczanowski R., Kucharczyk K. Novel KCNQ1 mutations in patients after myocardial infarction. Cardiology Journal. 2008;15(3), 252-260.Olszak-Waśkiewicz M., Dziuk M., Kubik L., Kaczanowski R., Kucharczyk K. Novel KCNQ1 mutations in patients after myocardial infarction. Cardiology Journal. 2008;15(3), 252-260.

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