Novel Genetic Variants Associated with Primary Myocardial Fibrosis in Sudden Cardiac Death Victims.
Genetics
Myocardial fibrosis
Sudden cardiac death
Journal
Journal of cardiovascular translational research
ISSN: 1937-5395
Titre abrégé: J Cardiovasc Transl Res
Pays: United States
ID NLM: 101468585
Informations de publication
Date de publication:
07 Jun 2024
07 Jun 2024
Historique:
received:
23
01
2024
accepted:
21
05
2024
medline:
7
6
2024
pubmed:
7
6
2024
entrez:
7
6
2024
Statut:
aheadofprint
Résumé
Myocardial fibrosis is a common finding in victims of sudden cardiac death (SCD). Whole exome sequencing was performed in 127 victims of SCD with primary myocardial fibrosis as the only pathological finding. These cases are derived from the Fingesture study which has collected data from autopsy-verified SCD victims in Northern Finland. A computational approach was used to identify protein interactions in cardiomyocytes. Associations of the identified variants with cardiac disease endpoints were investigated in the Finnish national genetic study (FinnGen) dataset. We identified 21 missense and one nonsense variant. Four variants were estimated to affect protein function, significantly associated with SCD/primary myocardial fibrosis (Fingesture) and associated with cardiac diseases in Finnish population (FinnGen). These variants locate in cartilage acidic protein 1 (CRATC1), calpain 1 (CAPN1), unc-45 myosin chaperone A (UNC45A) and unc-45 myosin chaperone B (UNC45B). The variants identified contribute to function of extracellular matrix and cardiomyocytes.
Identifiants
pubmed: 38848015
doi: 10.1007/s12265-024-10527-5
pii: 10.1007/s12265-024-10527-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Myerburg RJ, Goldberger JJ. Sudden Cardiac Arrest Risk Assessment: Population Science and the Individual Risk Mandate. JAMA Cardiol. 2017;2(6):689–94.
doi: 10.1001/jamacardio.2017.0266
pubmed: 28329250
Vahatalo J, Holmstrom L, Pakanen L, Kaikkonen K, Perkiomaki J, Huikuri H, et al. Coronary Artery Disease as the Cause of Sudden Cardiac Death Among Victims < 50 Years of Age. Am J Cardiol. 2021;147:33–8.
doi: 10.1016/j.amjcard.2021.02.012
pubmed: 33621522
Chery G, Kamp N, Kosinski AS, Schmidler GS, Lopes RD, Patel M, et al. Prognostic value of myocardial fibrosis on cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy: A systematic review. Am Heart J. 2020;229:52–60.
doi: 10.1016/j.ahj.2020.08.004
pubmed: 32916608
pmcid: 7417269
Di Marco A, Anguera I, Schmitt M, Klem I, Neilan TG, White JA, et al. Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy: Systematic Review and Meta-Analysis. JACC Heart Fail. 2017;5(1):28–38.
doi: 10.1016/j.jchf.2016.09.017
pubmed: 28017348
Bagnall RD, Weintraub RG, Ingles J, Duflou J, Yeates L, Lam L, et al. A Prospective Study of Sudden Cardiac Death among Children and Young Adults. N Engl J Med. 2016;374(25):2441–52.
doi: 10.1056/NEJMoa1510687
pubmed: 27332903
Rodriguez-Calvo MS, Brion M, Allegue C, Concheiro L, Carracedo A. Molecular genetics of sudden cardiac death. Forensic Sci Int. 2008;182(1-3):1–12.
doi: 10.1016/j.forsciint.2008.09.013
pubmed: 18992999
Hookana E, Junttila MJ, Puurunen VP, Tikkanen JT, Kaikkonen KS, Kortelainen ML, et al. Causes of nonischemic sudden cardiac death in the current era. Heart Rhythm. 2011;8(10):1570–5.
doi: 10.1016/j.hrthm.2011.06.031
pubmed: 21740887
Junttila MJ, Holmstrom L, Pylkas K, Mantere T, Kaikkonen K, Porvari K, et al. Primary Myocardial Fibrosis as an Alternative Phenotype Pathway of Inherited Cardiac Structural Disorders. Circulation. 2018;137(25):2716–26.
doi: 10.1161/CIRCULATIONAHA.117.032175
pubmed: 29915098
Khera AV, Mason-Suares H, Brockman D, Wang M, VanDenburgh MJ, Senol-Cosar O, et al. Rare Genetic Variants Associated With Sudden Cardiac Death in Adults. J Am Coll Cardiol. 2019;74(21):2623–34.
doi: 10.1016/j.jacc.2019.08.1060
pubmed: 31727422
pmcid: 7067308
Webster G, Puckelwartz MJ, Pesce LL, Dellefave-Castillo LM, Vanoye CG, Potet F, et al. Genomic autopsy of sudden deaths in young individuals. JAMA Cardiol. 2021;6(11):1247–56.
doi: 10.1001/jamacardio.2021.2789
pubmed: 34379075
Naba A, Clauser KR, Ding H, Whittaker CA, Carr SA, Hynes RO. The extracellular matrix: Tools and insights for the "omics" era. Matrix Biol. 2016;49:10–24.
doi: 10.1016/j.matbio.2015.06.003
pubmed: 26163349
Kaikkonen KS, Kortelainen ML, Linna E, Huikuri HV. Family history and the risk of sudden cardiac death as a manifestation of an acute coronary event. Circulation. 2006;114(14):1462–7.
doi: 10.1161/CIRCULATIONAHA.106.624593
pubmed: 17000909
Adolfsson E, Kling D, Gunnarsson C, Jonasson J, Green H, Green A. Whole exome sequencing of FFPE samples-expanding the horizon of forensic molecular autopsies. Int J Legal Med. 2023;137(4):1215–34.
doi: 10.1007/s00414-022-02906-x
pubmed: 36346469
Fuentes Fajardo KV, Adams D, Program NCS, Mason CE, Sincan M, Tifft C, et al. Detecting false-positive signals in exome sequencing. Hum Mutat. 2012;33(4):609–13.
doi: 10.1002/humu.22033
pubmed: 22294350
Kurki MI, Karjalainen J, Palta P, Sipila TP, Kristiansson K, Donner KM, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613(7944):508–18.
doi: 10.1038/s41586-022-05473-8
pubmed: 36653562
pmcid: 9849126
Barc J, Tadros R, Glinge C, Chiang DY, Jouni M, Simonet F, et al. Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility. Nat Genet. 2022;54(3):232–9.
doi: 10.1038/s41588-021-01007-6
pubmed: 35210625
pmcid: 9376964
Letsiou S, Manchado M, Zografaki M, Marka S, Anjos L, Skliros D, et al. Deciphering the role of cartilage protein 1 in human dermal fibroblasts: a transcriptomic approach. Funct Integr Genomics. 2021;21(3-4):503–11.
doi: 10.1007/s10142-021-00792-x
pubmed: 34269961
Thomas TP, Grisanti LA. The Dynamic Interplay Between Cardiac Inflammation and Fibrosis. Front Physiol. 2020;11:529075.
doi: 10.3389/fphys.2020.529075
pubmed: 33041853
pmcid: 7522448
Teng GZ, Dawson JF. The Dark Side of Actin: Cardiac actin variants highlight the role of allostery in disease development. Arch Biochem Biophys. 2020;695:108624.
doi: 10.1016/j.abb.2020.108624
pubmed: 33049292
Lindholm ME, Jimenez-Morales D, Zhu H, Seo K, Amar D, Zhao C, et al. Mono- and Biallelic Protein-Truncating Variants in Alpha-Actinin 2 Cause Cardiomyopathy Through Distinct Mechanisms. Circ Genom Precis Med. 2021;14(6):e003419.
doi: 10.1161/CIRCGEN.121.003419
pubmed: 34802252
pmcid: 8692448
Neuhof C, Neuhof H. Calpain system and its involvement in myocardial ischemia and reperfusion injury. World J Cardiol. 2014;6(7):638–52.
doi: 10.4330/wjc.v6.i7.638
pubmed: 25068024
pmcid: 4110612
Zheng D, Wang G, Li S, Fan GC, Peng T. Calpain-1 induces endoplasmic reticulum stress in promoting cardiomyocyte apoptosis following hypoxia/reoxygenation. Biochim Biophys Acta. 2015;1852(5):882–92.
doi: 10.1016/j.bbadis.2015.01.019
pubmed: 25660447
pmcid: 4418534
Patterson C, Portbury AL, Schisler JC, Willis MS. Tear me down: role of calpain in the development of cardiac ventricular hypertrophy. Circ Res. 2011;109(4):453–62.
doi: 10.1161/CIRCRESAHA.110.239749
pubmed: 21817165
pmcid: 3151485
Ho CY, Lopez B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P, et al. Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. N Engl J Med. 2010;363(6):552–63.
doi: 10.1056/NEJMoa1002659
pubmed: 20818890
pmcid: 3049917
Kachur TM, Pilgrim DB. Myosin assembly, maintenance and degradation in muscle: Role of the chaperone UNC-45 in myosin thick filament dynamics. Int J Mol Sci. 2008;9(9):1863–75.
doi: 10.3390/ijms9091863
pubmed: 19325835
pmcid: 2635755
Melkani GC, Bodmer R, Ocorr K, Bernstein SI. The UNC-45 chaperone is critical for establishing myosin-based myofibrillar organization and cardiac contractility in the Drosophila heart model. PLoS One. 2011;6(7):e22579.
doi: 10.1371/journal.pone.0022579
pubmed: 21799905
pmcid: 3143160
Landsverk ML, Li S, Hutagalung AH, Najafov A, Hoppe T, Barral JM, et al. The UNC-45 chaperone mediates sarcomere assembly through myosin degradation in Caenorhabditis elegans. J Cell Biol. 2007;177(2):205–10.
doi: 10.1083/jcb.200607084
pubmed: 17438072
pmcid: 2064129
Wang Q, Dhindsa RS, Carss K, Harper AR, Nag A, Tachmazidou I, et al. Rare variant contribution to human disease in 281,104 UK Biobank exomes. Nature. 2021;597(7877):527–32.
doi: 10.1038/s41586-021-03855-y
pubmed: 34375979
pmcid: 8458098
Wilde AAM, Semsarian C, Marquez MF, Shamloo AS, Ackerman MJ, Ashley EA, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases. Europace. 2022;24(8):1307–67.
doi: 10.1093/europace/euac030
pubmed: 35373836
pmcid: 9435643
Stiles MK, Wilde AAM, Abrams DJ, Ackerman MJ, Albert CM, Behr ER, et al. 2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families. J Arrhythm. 2021;37(3):481–534.
doi: 10.1002/joa3.12449
pubmed: 34141003
pmcid: 8207384