1. На главную
  2. Электронные версии
  3. Генетика
  4. T. 59, № 6, 2023

Генетика, 2023, T. 59, № 6, стр. 615-632

Патогенетика кардиомиопатий

А. Н. Кучер 1, А. А. Слепцов 1, М. С. Назаренко 1, *

1 Научно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наук
634050 Томск, Россия

* E-mail: maria.nazarenko@medgenetics.ru

Поступила в редакцию 22.08.2022
После доработки 28.10.2022
Принята к публикации 22.11.2022

Аннотация

Анализируется значимость генетических факторов в развитии как первичных (или менделевских) кардиомиопатий (КМП), так и некоторых вторичных (приобретенных) форм КМП. Для первичных КМП описаны десятки генов с патогенными/вероятно патогенными вариантами. В большинстве случаев спектр причинных генетических вариантов для разных КМП специфичен, но регистрируются также общие гены и варианты. При этом, с одной стороны, не для всех случаев первичных КМП установлены генетические причины заболеваний, а с другой, патогенные варианты в генах менделевских КМП регистрируются и при вторичных КМП. Генетический компонент в развитии и первичных и вторичных КМП установлен также при проведении широкогеномных ассоциативных исследований (GWAS). Однонуклеотидные варианты (SNPs), ассоциированные и с первичными, и со вторичными КМП, в большинстве случаев специфичны для разных КМП и вносят небольшой вклад в риск развития патологий. Для некоторых SNPs установлены ассоциации с ЭКГ- и Эхо-кардиографическими параметрами морфологически неизмененного сердца у человека. Большинство из SNPs, ассоциированных с КМП по данным GWAS, локализованы в некодирующих участках генома, но обладают регуляторным потенциалом, выступая в ткани сердца в качестве локусов, влияющих на уровень экспрессии (eQTL), сплайсинг (sQTL) или эпигенетические модификации. Примечательно, что эффекты генотипов eQTL и sQTL в ряде случаев неравнозначны для различных анатомических отделов сердца. В целом фенотип и клиническая картина КМП могут определяться широким спектром редких патогенных/вероятно патогенных вариантов с сильным эффектом и частых высокополиморфных вариантов с небольшим эффектом и модифицироваться эпигенетическими факторами.

Ключевые слова: кардиомиопатия, патогенетика, гены моногенных кардиомиопатий, широкогеномные ассоциативные исследования.

Список литературы

  1. McKenna W.J., Maron B.J., Thiene G. Classification, epidemiology, and global burden of cardiomyopathies // Circ. Res. 2017. V. 121. № 7. P. 722–730. https://doi.org/10.1161/CIRCRESAHA.117.309711

  2. Salemi V.M.C., Mohty D., Altavila S.L.L. et al. Insights into the classification of cardiomyopathies: past, present, and future directions // Clinics (Sao Paulo). 2021. V. 76. Р. e2808. https://doi.org/10.6061/clinics/2021/e2808

  3. McKenna W.J., Judge D.P. Epidemiology of the inherited cardiomyopathies // Nat. Rev. Cardiol. 2021. V. 18. № 1. P. 22–36. https://doi.org/10.1038/s41569-020-0428-2

  4. Ommen S.R., Mital S., Burke M.A. et al. AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines // Circulation. 2020. V. 142. Iss. 25. Р. e558–e631. https://doi.org/10.1161/CIR.0000000000000937

  5. Corrado D., Link M.S., Calkins H. Arrhythmogenic right ventricular cardiomyopathy // N. Engl. J. Med. 2017. V. 376. № 1. P. 61–72. https://doi.org/10.1056/NEJMra1509267

  6. Ciarambino T., Menna G., Sansone G., Giordano M. Cardiomyopathies: an overview // Int. J. Mol. Sci. 2021. V. 22. Iss. 14. https://doi.org/10.3390/ijms22147722

  7. Hey T.M., Rasmussen T.B., Madsen T. et al. Clinical and genetic investigations of 109 index patients with dilated cardiomyopathy and 445 of their relatives // Circ. Heart Fail. 2020. V. 13. № 10. Р. e006701. https://doi.org/10.1161/circheartfailure.119.006701

  8. Robertson J., Lindgren M., Schaufelberger M. et al. Body mass index in young women and risk of cardiomyopathy: A long-term follow-up study in Sweden // Circulation. 2020. V. 141. Iss. 7. P. 520–529. https://doi.org/10.1161/circulationaha.119.044056

  9. Peters S., Johnson R., Birch S. et al. Familial dilated cardiomyopathy // Heart Lung Circ. 2020. V. 29. Iss. 4. P. 566–574. https://doi.org/10.1016/j.hlc.2019.11.018

  10. Замараева Д.В., Трунина И.И., Котлукова Н.П. и др. Дебют генетически обусловленной дилатационной кардиомиопатии в исходе перенесенного миокардита (клинический случай) // Клин. и эксперим. хирургия. Журн. им. акад. Б.В. Петровского. 2020. Т. 8. № 3(29). С. 110–118. https://doi.org/10.33029/2308-1198-2020-8-3-110-118

  11. Povysil G., Chazara O., Carss K.J. et al. Assessing the role of rare genetic variation in patients with heart failure // JAMA Cardiol. 2021. V. 6. № 4. e206500. https://doi.org/10.1001/jamacardio.2020.6500

  12. Tiron C., Campuzano O., Fernández-Falgueras A. et al. Prevalence of pathogenic variants in cardiomyopathy-associated genes in myocarditis // Circ. Genom Precis. Med. 2022. V. 15. № 3. https://doi.org/10.1161/CIRCGEN.121.003408

  13. Patel A.P., Dron J.S., Wang M. et al. Association of pathogenic DNA variants predisposing to cardiomyopathy with cardiovascular disease outcomes and all-cause mortality // JAMA Cardiol. 2022. V. 7. № 7. P. 723–732. https://doi.org/10.1001/jamacardio.2022.0901

  14. Lazarte J., Jurgens S.J., Choi S.H. et al. LMNA variants and risk of adult-onset cardiac disease // J. Am. Coll. Cardiol. 2022. V. 80. № 1. P. 50–59. https://doi.org/10.1016/j.jacc.2022.04.035

  15. Cipriani A., Perazzolo Marra M., Bariani R. et al. Differential diagnosis of arrhythmogenic cardiomyopathy: phenocopies versus disease variants // Minerva Med. 2021. V. 112. № 2. P. 269–280. https://doi.org/10.23736/S0026-4806.20.06782-8

  16. Mattesi G., Cipriani A., Bauce B. et al. Arrhythmogenic left ventricular cardiomyopathy: Genotype-phenotype correlations and new diagnostic criteria // J. Clin. Med. 2021. V. 10. Iss. 10. https://doi.org/10.3390/jcm10102212

  17. Lee T.M., Hsu D.T., Kantor P. et al. Pediatric cardiomyopathies // Circ. Res. 2017. V. 21. № 7. P. 855–873. https://doi.org/10.1161/CIRCRESAHA.116.309386

  18. Лутохина Ю.А., Благова О.В., Шестак А.Г. и др. Сочетание аритмогенной дисплазии правого желудочка и некомпактного миокарда левого желудочка как особая форма кардиомиопатии: клиника, диагностика, генетическая природа, течение // Вестн. РАМН. 2020. Т. 75. № 6. С. 594–604. https://doi.org/10.15690/vramn1245

  19. Blagova O., Alieva I., Kogan E. et al. Mixed hypertrophic and dilated phenotype of cardiomyopathy in a patient with homozygous in-frame deletion in the MYBPC3 gene treated as myocarditis for a long time // Front. Pharmacol. 2020. V. 11. https://doi.org/10.3389/fphar.2020.579450

  20. Jefferies J.L., Wilkinson J.D., Sleeper L.A. et al. Cardiomyopathy phenotypes and outcomes for children with left ventricular myocardial noncompaction: results from the Pediatric Cardiomyopathy Registry // J. Card. Fail. 2015. V. 21. № 1. P. 877–884. https://doi.org/10.1016/j.cardfail.2015.06.381

  21. Webber S.A., Lipshultz S.E., Sleeper L.A. et al. Outcomes of restrictive cardiomyopathy in childhood and the influence of phenotype: A report from the Pediatric Cardiomyopathy Registry // Circulation. 2012. V. 126. Iss. 10. P. 1237–1244. https://doi.org/10.1161/CIRCULATIONAHA.112.104638

  22. Lipshultz S.E., Orav E.J., Wilkinson J.D. et al. Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: An analysis of data from the Pediatric Cardiomyopathy Registry // Lancet. 2013. V. 382. № 9908. P. 1889–1897. https://doi.org/10.1016/S0140-6736(13)61685-2

  23. Кучер А.Н., Валиахметов Н.Р., Салахов Р.Р. и др. Фенотипическая вариабельность гипертрофической кардиомиопатии у носителей патогенного варианта p.Arg870His гена MYH7 // Бюл. сиб. медицины. 2022. Т. 21. № 3. С. 205–216. https://doi.org/10.20528/1682-0363-2022-3-205-216

  24. Кучер А.Н., Слепцов А.А., Назаренко М.С. Генетический ландшафт дилатационной кардиомиопатии // Генетика. 2022. Т. 58. № 4. С. 371–387. https://doi.org/10.31857/S0016675822030080

  25. Menon S.C., Michels V.V., Pellikka P.A. et al. Cardiac troponin T mutation in familial cardiomyopathy with variable remodeling and restrictive physiology // Clin. Genet. 2008. V. 74. Iss. 5. P. 445–454. https://doi.org/10.1111/j.1399-0004.2008.01062.x

  26. Norrish G., Cleary A., Field E. et al. Clinical features and natural history of preadolescent nonsyndromic hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. 2022. V. 79. № 20. P. 1986–1997. https://doi.org/10.1016/j.jacc.2022.03.347

  27. Wu W., Lu C.X., Wang Y.N. et al. Novel phenotype–genotype correlations of restrictive cardiomyopathy with myosin-binding protein c (MYBPC3) gene mutations tested by next-generation sequencing // J. Am. Heart Assoc. 2015. V. 4. № 7.https://doi.org/10.1161/JAHA.115.001879

  28. Курушко Т.В., Вайханская Т.Г., Булгак А.Г. и др. Ламин A/C ассоциированная дилатационная кардиомиопатия: вариабельность клинических проявлений // Кардиология в Беларуси. 2018. Т. 10. № 6. С. 892–903.

  29. Simple ClinVar [Electronic resource]. URL: https://simple-clinvar.broadinstitute.org/. Accessed 03.2022.

  30. Pérez-Palma E., Gramm M., Nürnberg P. et al. Simple ClinVar: An interactive web server to explore and retrieve gene and disease variants aggregated in ClinVar database // Nucl. Acids Res. 2019. V. 47. № W1. P. W99–W105. https://doi.org/10.1093/nar/gkz411

  31. Salman O.F., El-Rayess H.M., Abi Khalil C. et al. Inherited cardiomyopathies and the role of mutations in non-coding regions of the genome // Front. Cardiovasc. Med. 2018. V. 5. № 77. https://doi.org/10.3389/fcvm.2018.00077

  32. Комиссарова С.М., Чакова Н.Н., Ниязова С.С. Гипертрофическая кардиомиопатия: анализ связи генотипа и фенотипа у пациентов с высоким риском внезапной смерти // Мед. генетика. 2018. Т. 17. № 11. С. 34–42.

  33. Walsh R., Offerhaus J.A., Tadros R., Bezzina C.R. Minor hypertrophic cardiomyopathy genes, major insights into the genetics of cardiomyopathies // Nat. Rev. Cardiol. 2022. V. 9. № 3. P. 151–167. https://doi.org/10.1038/s41569-021-00608-2

  34. Ingles J., Goldstein J., Thaxton C. et al. Evaluating the clinical validity of hypertrophic cardiomyopathy genes // Circ. Genom. Precis. Med. 2019. V. 12. № 2. https://doi.org/10.1161/CIRCGEN.119.002460

  35. Zigova M., Bernasovska J., Boronova I. et al. Finding the candidate sequence variants for diagnosis of hypertrophic cardiomyopathy in East Slovak patients // J. Clin. Lab. Anal. 2018. V. 32. № 3. https://doi.org/10.1002/jcla.22303

  36. Richmond C.M., James P.A., Pantaleo S. et al. Clinical and laboratory reporting impact of ACMG-AMP and modified ClinGen variant classification frameworks in MYH7-related cardiomyopathy // Genet. Med. 2021. V. 23. Iss. 6. P. 1108–1115. https://doi.org/10.1038/s41436-021-01107-y

  37. Kubo T., Gimeno J.R., Bahl A. et al. Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype // J. Am. Coll. Cardiol. 2007. V. 49. № 25. P. 2419–2426. https://doi.org/10.1016/j.jacc.2007.02.061

  38. Vio R., Angelini A., Basso C. et al. Hypertrophic cardiomyopathy and primary restrictive cardiomyopathy: similarities, differences and phenocopies // J. Clin. Med. 2021. V. 10. № 9. Article 1954. https://doi.org/10.3390/jcm10091954

  39. Li S., Wu B., Yin G. et al. MRI characteristics, prevalence, and outcomes of hypertrophic cardiomyopathy with restrictive phenotype // Radiol. Cardiothorac. Imaging. 2020. V. 2. № 4. Р. e190158. https://doi.org/10.1148/ryct.2020190158

  40. Hershberger R.E., Jordan E. Dilated Cardiomyopathy Overview. 2007 Jul 27 [updated 2022 Apr 7] // Gene-Reviews® [Internet] / Eds Adam M.P., Ardinger H.H., Pagon R.A. et al. Seattle (WA): Univ. Washington, Seattle, 1993–2022.

  41. Towbin J.A., McKenna W.J., Abrams D.J. et al. HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy // Heart Rhythm. 2019. V. 16. № 11. P. e301–e372. https://doi.org/10.1016/j.hrthm.2019.05.007

  42. Groeneweg J.A., Bhonsale A., James C.A. et al. Clinical presentation, long-term follow-up, and outcomes of 1001 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients and family members // Circ. Cardiovasc. Genet. 2015. V. 8. № 3. P. 437–446. https://doi.org/10.1161/CIRCGENETICS.114.001003

  43. Pugh T.J., Kelly M.A., Gowrisankar S. et al. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing // Genet. Med. 2014. V. 16. Iss. 8. P. 601–608. https://doi.org/10.1038/gim.2013.204

  44. Jordan E., Hershberger R.E. Considering complexity in the genetic evaluation of dilated cardiomyopathy // Heart. 2021. V. 107. № 2. P. 106–112. https://doi.org/10.1136/heartjnl-2020-316658

  45. Morales A., Kinnamon D.D., Jordan E. et al. Variant Interpretation for Dilated Cardiomyopathy: Refinement of the American College of Medical Genetics and Genomics/ClinGen Guidelines for the DCM Precision Medicine Study // Circ. Genom. Precis. Med. 2020. V. 13. № 2. https://doi.org/10.1161/CIRCGEN.119.002480

  46. Lopes L.R., Zekavati A., Syrris P. et al. Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing // J. Med. Genet. 2013. V. 50. № 4. P. 228–239. https://doi.org/10.1136/jmedgenet-2012-101270

  47. Tran Vu M.T., Nguyen T.V., Huynh N.V. et al. Presence of hypertrophic cardiomyopathy related gene mutations and clinical manifestations in Vietnamese patients with hypertrophic cardiomyopathy // Circ. J. 2019. V. 83. № 9. P. 1908–1916. https://doi.org/10.1253/circj.CJ-19-0190

  48. Harper A.R., Goel A., Grace C. et al. Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity // Nat. Genet. 2021. V. 53. № 2. P. 135–142. https://doi.org/10.1038/s41588-020-00764-0

  49. Villard E., Perret C., Gary F. et al. A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy // Eur. Heart J. 2011. V. 32. Iss. 9. P. 1065–1076. https://doi.org/10.1093/eurheartj/ehr105

  50. Meder B., Rühle F., Weis T. et al. A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy // Eur. Heart J. 2014. V. 35. Iss. 16. P. 1069–1077. https://doi.org/10.1093/eurheartj/eht251

  51. Xu H., Dorn G.W. 2nd, Shetty A. et al. A Genome-wide association study of idiopathic dilated cardiomyopathy in African Americans // J. Pers. Med. 2018. V. 8. № 1. Article 11. https://doi.org/10.3390/jpm8010011

  52. de Denus S., Mottet F., Korol S. et al. A genetic association study of heart failure: More evidence for the role of BAG3 in idiopathic dilated cardiomyopathy // ESC Heart Fail. 2020. V. 7. № 6. P. 4384–4389. https://doi.org/10.1002/ehf2.12934

  53. Garnier S., Harakalova M., Weiss S. et al. Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23 // Eur. Heart J. 2021. V. 42. Iss. 20. P. 2000–2011. https://doi.org/10.1093/eurheartj/ehab030

  54. Deng X., Sabino E.C., Cunha-Neto E. et al. Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects // PLoS One. 2013. V. 8. № 11. Р. e79629. https://doi.org/10.1371/journal.pone.0079629

  55. Casares-Marfil D., Strauss M., Bosch-Nicolau P. et al. A genome-wide association study identifies novel susceptibility loci in chronic chagas cardiomyopathy // Clin. Infect. Dis. 2021. V. 73. № 4. P. 672–679. https://doi.org/10.1093/cid/ciab090

  56. Eitel I., Moeller C., Munz M. et al. Genome-wide association study in takotsubo syndrome – Preliminary results and future directions // Int. J. Cardiol. 2017. V. 236. P. 335–339. https://doi.org/10.1016/j.ijcard.2017.01.093

  57. López-Mejías R., Carmona F.D., Genre F. et al. Identification of a 3'-untranslated genetic variant of RARB associated with carotid intima-media thickness in rheumatoid arthritis: A Genome-Wide Association Study // Arthritis Rheumatol. 2019. V. 71. № 3. P. 351–360. https://doi.org/10.1002/art.40734

  58. Wang X., Sun C.L., Quiñones-Lombraña A. et al. CELF4 variant and anthracycline-related cardiomyopathy: A Children’s Oncology Group Genome-Wide Association Study // J. Clin. Oncol. 2016. V. 34. Iss. 8. P. 863–870. https://doi.org/10.1200/JCO.2015.63.4550

  59. Horne B.D., Rasmusson K.D., Alharethi R. et al. Genome-wide significance and replication of the chromosome 12p11.22 locus near the PTHLH gene for peripartum cardiomyopathy // Circ. Cardiovasc. Genet. 2011. V. 4. № 4. P. 359–366. https://doi.org/10.1161/CIRCGENETICS.110.959205

  60. GWAS Catalog [Electronic resource]. URL: https://www.ebi.ac.uk/gwas/. Accessed 05.2022.

  61. Tadros R., Francis C., Xu X. et al. Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect // Nat. Genet. 2021. V. 53. № 2. P. 128–134. https://doi.org/10.1038/s41588-020-00762-2

  62. UCSC Genome Browser on Human (GRCh38/hg38) https://genome.ucsc.edu/.

  63. VannoPortal Index [Electronic resource]. URL: http://www.mulinlab.org/vportal/index.html/. Accessed 05.2022.

  64. National Center for Biotechnology Information Electronic resource]. URL: https://www.ncbi.nlm.nih.gov/. Accessed 06.2022.

  65. Genotype-Tissue Expression (GTEx) Portal [Electronic resource]. URL: https://gtexportal.org/home/. Accessed 06.2022.

  66. Ahn J., Wu H., Lee K. Integrative analysis revealing human heart-specific genes and consolidating heart-related phenotypes // Front Genet. 2020. V. 11.https://doi.org/10.3389/fgene.2020.00777

  67. Hammond C.M., Bao H., Hendriks I.A. et al. DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network // Mol. Cell. 2021. V. 81. № 12. P. 2533–2548.e9. https://doi.org/10.1016/j.molcel.2021.03.041

  68. Кучер А.Н., Назаренко М.С. Регуляторный потенциал ко-локализованных с генами кардиомиопатий некодирующих РНК // Генетика. 2023. Т. 59. № 4. С. 381–402.

  69. Кучер А.Н., Назаренко М.С. Эпигенетика кардиомиопатий: модификации гистонов и метилирование ДНК // Генетика. 2023. Т. 59. № 3. С. 266–282.

  70. Scolari F.L., Faganello L.S., Garbin H.I. et al. A systematic review of microRNAs in patients with hypertrophic cardiomyopathy // Int. J. Cardiol. 2021. V. 327. P. 146–154. https://doi.org/10.1016/j.ijcard.2020.11.004

  71. Gao J., Collyer J., Wang M. et al. Genetic dissection of hypertrophic cardiomyopathy with myocardial RNA-Seq // Int. J. Mol. Sci. 2020. V. 21. № 9. https://doi.org/10.3390/ijms21093040

  72. Huang G., Liu J., Yang C. et al. RNA sequencing discloses the genome wide profile of long noncoding RNAs in dilated cardiomyopathy // Mol. Med. Rep. 2019. V. 19. № 4. P. 2569–2580. https://doi.org/10.3892/mmr.2019.9937

  73. Hailu F.T., Karimpour-Fard A., Toni L.S. et al. Integrated analysis of miRNA-mRNA interaction in pediatric dilated cardiomyopathy // Pediatr. Res. 2022. V. 92. № 1. P. 98–108. https://doi.org/10.1038/s41390-021-01548-w

  74. Ensembl Genome Browser [Electronic resource]. URL: https://www.ensembl.org/index.html/. Accessed 06.2022.

  75. Su X., Lv L., Li Y. et al. lncRNA MIRF promotes cardiac apoptosis through the miR-26a-Bak1 axis // Mol. Ther. Nucl. Acids. 2020. V. 20. P. 841–850. https://doi.org/10.1016/j.omtn.2020.05.002

  76. Liu Y., Liu N., Bai F., Liu Q. Identifying ceRNA networks associated with the susceptibility and persistence of atrial fibrillation through weighted gene co-expression network analysis // Front. Genet. 2021. V. 12. https://doi.org/10.3389/fgene.2021.653474

  77. Esslinger U., Garnier S., Korniat A. et al. Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy // PLoS One. 2017. V. 12. № 3. https://doi.org/10.1371/journal.pone.0172995

  78. Ochoa J.P., Sabater-Molina M., García-Pinilla J.M. et al. Formin homology 2 domain containing 3 (FHOD3) is a genetic basis for hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. 2018. V. 72. № 20. P. 2457–2467. https://doi.org/10.1016/j.jacc.2018.10.001

  79. Wu G., Ruan J., Liu J. et al. Variant spectrum of formin homology 2 domain-containing 3 gene in Chinese patients with hypertrophic cardiomyopathy // J. Am. Heart Assoc. 2021. V. 10. № 5. https://doi.org/10.1161/JAHA.120.018236

  80. Fernlund E., Kissopoulou A., Green H. et al. Hereditary hypertrophic cardiomyopathy in children and young adults – the value of reevaluating and expanding gene panel analyses // Genes (Basel). 2020. V. 11. № 12. https://doi.org/10.3390/genes11121472

  81. Qin X., Li P., Qu H.Q. et al. FLNC and MYLK2 gene mutations in a Chinese family with different phenotypes of cardiomyopathy // Int. Heart J. 2021. V. 62. № 1. P. 127–134. https://doi.org/10.1536/ihj.20-351

  82. Brun F., Gigli M., Graw S.L. et al. FLNC truncations cause arrhythmogenic right ventricular cardiomyopathy // J. Med. Genet. 2020. V. 57. № 4. P. 254–257. https://doi.org/10.1136/jmedgenet-2019-106394

  83. Xiao F., Wei Q., Wu B. et al. Clinical exome sequencing revealed that FLNC variants contribute to the early diagnosis of cardiomyopathies in infant patients // Transl. Pediatr. 2020. V. 9. № 1. P. 21–33. https://doi.org/10.21037/tp.2019.12.02

  84. Phelan D.G., Anderson D.J., Howden S.E. et al. ALPK3-deficient cardiomyocytes generated from patient-derived induced pluripotent stem cells and mutant human embryonic stem cells display abnormal calcium handling and establish that ALPK3 deficiency underlies familial cardiomyopathy // Eur. Heart J. 2016. V. 37. Iss. 33. P. 2586–2590. https://doi.org/10.1093/eurheartj/ehw160

  85. Herkert J.C., Verhagen J.M.A., Yotti R. et al. Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants // Am. Heart. J. 2020. V. 225. P. 108–119. https://doi.org/10.1016/j.ahj.2020.03.023

  86. Lopes L.R., Garcia-Hernández S., Lorenzini M. et al. Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy // Eur. Heart J. 2021. V. 42. Iss. 32. P. 3063–3073. https://doi.org/10.1093/eurheartj/ehab424

  87. Wooten E.C., Hebl V.B., Wolf M.J. et al. Formin homology 2 domain containing 3 variants associated with hypertrophic cardiomyopathy // Circ. Cardiovasc. Genet. 2013. V. 6. № 1. P. 10–18. https://doi.org/10.1161/CIRCGENETICS.112.965277

  88. Kan-O M., Takeya R., Abe T. et al. Mammalian formin Fhod3 plays an essential role in cardiogenesis by organizing myofibrillogenesis // Biol. Open. 2012. V. 1. № 9. P. 889–896. https://doi.org/10.1242/bio.20121370

  89. Fujimoto N., Kan-O M., Ushijima T. et al. Transgenic expression of the formin protein Fhod3 selectively in the embryonic heart: Role of actin-binding activity of Fhod3 and its sarcomeric localization during myofibrillogenesis // PLoS One. 2016. V. 11. № 2.https://doi.org/10.1371/journal.pone.0148472

  90. Ushijima T., Fujimoto N., Matsuyama S. et al. The actin-organizing formin protein Fhod3 is required for postnatal development and functional maintenance of the adult heart in mice // J. Biol. Chem. 2018. V. 293. Iss. 1. P. 148–162. https://doi.org/10.1074/jbc.M117.813931

  91. Matsuyama S., Kage Y., Fujimoto N. et al. Interaction between cardiac myosin-binding protein C and formin Fhod3 // Proc. Natl Acad. Sci. USA. 2018. V. 115. Iss. 19. P. E4386–E4395. https://doi.org/10.1073/pnas.1716498115

  92. Arimura T., Takeya R., Ishikawa T. et al. Dilated cardiomyopathy-associated FHOD3 variant impairs the ability to induce activation of transcription factor serum response factor // Circ. J. 2013. V. 77. № 12. P. 2990–2996. https://doi.org/10.1253/circj.cj-13-0255

  93. Myasnikov R., Bukaeva A., Kulikova O. et al. A case of severe left-ventricular noncompaction associated with splicing altering variant in the FHOD3 gene // Genes (Basel). 2022. V. 13. № 2. https://doi.org/10.3390/genes13020309

  94. Antoku S., Wu W., Joseph L.C. et al. ERK1/2 phosphorylation of FHOD connects signaling and nuclear positioning alternations in cardiac laminopathy // Dev. Cell. 2019. V. 51. № 5. P. 602–616.e12. https://doi.org/10.1016/j.devcel.2019.10.023

  95. Verdonschot J.A.J., Vanhoutte E.K., Claes G.R.F. et al. A mutation update for the FLNC gene in myopathies and cardiomyopathies // Hum. Mutat. 2020. V. 41. Iss. 6. P. 1091–1111. https://doi.org/10.1002/humu.24004

  96. Ortiz-Genga M.F., Cuenca S., Dal Ferro M. et al. Truncating FLNC mutations are associated with high-risk dilated and arrhythmogenic cardiomyopathies // J. Am. Coll. Cardiol. 2016. V. 68. № 22. P. 2440–2451. https://doi.org/10.1016/j.jacc.2016.09.927

  97. Begay R.L., Tharp C.A., Martin A. et al. FLNC gene splice mutations cause dilated cardiomyopathy // JACC Basic Transl. Sci. 2016. V. 1. № 5. P. 344–359. https://doi.org/10.1016/j.jacbts.2016.05.004

  98. Hall C.L., Gurha P., Sabater-Molina M. et al. RNA sequencing-based transcriptome profiling of cardiac tissue implicates novel putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy // Int. J. Cardiol. 2020. V. 302. P. 124–130. https://doi.org/10.1016/j.ijcard.2019.12.002

  99. Goli R., Li J., Brandimarto J. et al. Genetic and phenotypic landscape of peripartum cardiomyopathy // Circulation. 2021. V. 143. Iss. 19. P. 1852–1862. https://doi.org/10.1161/CIRCULATIONAHA.120. 052395

  100. Ito S., Asakura M., Liao Y. et al. Identification of the Mtus1 splice variant as a novel inhibitory factor against cardiac hypertrophy // J. Am. Heart Assoc. 2016. V. 5. № 7. https://doi.org/10.1161/JAHA.116.003521

  101. Parvatiyar M.S., Brownstein A.J., Kanashiro-Takeuchi R.M. et al. Stabilization of the cardiac sarcolemma by sarcospan rescues DMD-associated cardiomyopathy // JCI Insight. 2019. V. 5. № 11. https://doi.org/10.1172/jci.insight.123855

  102. Stark K., Esslinger U.B., Reinhard W. et al. Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy // PLoS Genet. 2010. V. 6. № 10. https://doi.org/10.1371/journal.pgen.1001167

  103. Стрельцова А.А., Гудкова А.Я., Полякова А.А. и др. Полиморфный вариант rs1739843 гена белка теплового шока 7 (HSPB7) и его связь с вариантами клинического течения и исходами у пациентов с гипертрофической кардиомиопатией (результаты 10-летнего наблюдения) // Рос. кардиол. журн. 2019. № 10. С. 7–15. https://doi.org/10.15829/1560-4071-2019-10-7-15

  104. Clausen A.G., Vad O.B., Andersen J.H., Olesen M.S. Loss-of-function variants in the SYNPO2L gene are associated with atrial fibrillation // Front. Cardiovasc. Med. 2021. V. 8. Article 650667. https://doi.org/10.3389/fcvm.2021.650667

  105. Hsu J., Gore-Panter S., Tchou G. et al. Genetic control of left atrial gene expression yields insights into the genetic susceptibility for atrial fibrillation // Circ. Genom Precis. Med. 2018. V. 11. № 3. https://doi.org/10.1161/CIRCGEN.118.002107

  106. Ma X., Mo C., Huang L. et al. An robust rank aggregation and least absolute shrinkage and selection operator analysis of novel gene signatures in dilated cardiomyopathy // Front. Cardiovasc. Med. 2021. V. 8. https://doi.org/10.3389/fcvm.2021.747803

  107. Aragam K.G., Chaffin M., Levinson R.T. et al. Phenotypic refinement of heart failure in a national biobank facilitates genetic discovery // Circulation. 2019. V. 139. P. 489–501. https://doi.org/10.1161/CIRCULATIONAHA.118.0-35774

  108. Celeghin R., Cipriani A., Bariani R. et al. Filamin-C variant-associated cardiomyopathy: A pooled analysis of individual patient data to evaluate the clinical profile and risk of sudden cardiac death // Heart Rhythm. 2022. V. 19. № 2. P. 235–243. https://doi.org/10.1016/j.hrthm.2021.09.029

  109. Finocchiaro G., Merlo M., Sheikh N. et al. The electrocardiogram in the diagnosis and management of patients with dilated cardiomyopathy // Eur. J. Heart Fail. 2020. V. 22. Iss. 7. P. 1097–1107. https://doi.org/10.1002/ejhf.1815

  110. Lee Y., Choi B., Lee M.S. et al. An artificial intelligence electrocardiogram analysis for detecting cardiomyopathy in the peripartum period // Int. J. Cardiol. 2022. V. 352. P. 72–77. https://doi.org/10.1016/j.ijcard.2022.01.064

  111. Yoneda Z.T., Anderson K.C., Quintana J.A. et al. Early-onset atrial fibrillation and the prevalence of rare variants in cardiomyopathy and arrhythmia genes // JAMA Cardiol. 2021. V. 6. № 12. P. 1371–1379. https://doi.org/10.1001/jamacardio.2021.3370

  112. Verweij N., Benjamins J.W., Morley M.P. et al. The genetic makeup of the electrocardiogram // Cell Syst. 2020. V. 11. Iss. 3. P. 229–238.e5. https://doi.org/10.1016/j.cels.2020.08.005

  113. Weng L.C., Hall A.W., Choi S.H. et al. Genetic determinants of electrocardiographic P-wave duration and relation to atrial fibrillation // Circ. Genom. Precis. Med. 2020. V. 13. № 5. P. 387–395. https://doi.org/10.1161/CIRCGEN.119.002874

  114. Liao W.C., Juo L.Y., Shih Y.L. et al. HSPB7 prevents cardiac conduction system defect through maintaining intercalated disc integrity // PLoS Genet. 2017. V. 13. № 8. https://doi.org/10.1371/journal.pgen.1006984

  115. Ke L., Meijering R.A., Hoogstra-Berends F. et al. HSPB1, HSPB6, HSPB7 and HSPB8 protect against RhoA GTPase-induced remodeling in tachypaced atrial myocytes // PLoS One. 2011. V. 6. № 6.https://doi.org/10.1371/journal.pone.0020395

  116. Adriaens M.E., Lodder E.M., Moreno-Moral A. et al. Systems genetics approaches in rat identify novel genes and gene networks associated with cardiac conduction // J. Am. Heart Assoc. 2018. V. 7. № 21. https://doi.org/10.1161/JAHA.118.009243

  117. Pirruccello J.P., Bick A., Wang M. et al. Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy // Nat. Commun. 2020. V. 11. № 1. Article 2254. https://doi.org/10.1038/s41467-020-15823-7

  118. Biddinger K.J., Jurgens S.J., Maamari D. et al. Rare and common genetic variation underlying the risk of hypertrophic cardiomyopathy in a National Biobank // JAMA Cardiol. 2022. V. 7. № 7. P. 715–722. https://doi.org/10.1001/jamacardio.2022.1061

  119. Marian A.J. Oligogenic cardiomyopathy // J. Cardiovasc. Aging. 2022. V. 2. Article 3. https://doi.org/10.20517/jca.2021.27

  120. Pourebrahim K., Marian J.G., Tan Y. et al. A combinatorial oligogenic basis for the phenotypic plasticity between late-onset dilated and arrhythmogenic cardiomyopathy in a single family // J. Cardiovasc. Aging. 2021. V. 1. Article 12. https://doi.org/10.20517/jca.2021.15

  121. Баулина Н.М., Киселёв И.С., Чумакова О.С., Фаворова О.О. Гипертрофическая кардиомиопатия как олигогенное заболевание: аргументы транскриптомики // Мол. биология. 2020. Т. 54. № 6. С. 955–967. https://doi.org/10.31857/S0026898420060026

  122. Alimohamed M.Z., Johansson L.F., Posafalvi A. et al. Diagnostic yield of targeted next generation sequencing in 2002 Dutch cardiomyopathy patients // Int. J. Cardiol. 2021. V. 332. P. 99–104. https://doi.org/10.1016/j.ijcard.2021.02.069

Дополнительные материалы

скачать ESM.docx
Приложение 1.
Таблица 1. Характеристика однонуклеотидных полиморфизмов (SNPs), ассоциированных с кардиомиопатиями (КМП) по данным GWAS
Таблица 2. Регуляторный потенциал однонуклеотидных полиморфизмов (SNPs), ассоциированных с различными кардиомиопатиями (КМП), по данным GWAS [ebi.ac.uk/gwas/] и GTEx [gtexportal.org]

Инструменты

следующая статья выпуска содержание выпуска

Генетика

Архивы выпусков Информация о журнале Отправить рукопись в журнал