Analysis of the Association Between Copy Number Variation and Ventricular Fibrillation in ST-Elevation Acute Myocardial Infarction

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Mar 13

PMID 38473795

Authors

Roberto Lorente-Bermudez

Ricardo Pan-Lizcano

Lucia Nunez

Domingo Lopez-Vazquez

Fernando Rebollal-Leal

Jose Manuel Vazquez-Rodriguez

Manuel Hermida-Prieto

Affiliations

Soon will be listed here.

Abstract

Sudden cardiac death due to ventricular fibrillation (VF) during ST-elevation acute myocardial infarction (STEAMI) significantly contributes to cardiovascular-related deaths. Although VF has been linked to genetic factors, variations in copy number variation (CNV), a significant source of genetic variation, have remained largely unexplored in this context. To address this knowledge gap, this study performed whole exome sequencing analysis on a cohort of 39 patients with STEAMI who experienced VF, aiming to elucidate the role of CNVs in this pathology. The analysis revealed CNVs in the form of duplications in the and genes as well as CNVs in the form of deletions in the and genes, which could potentially serve as risk indicators for VF during STEAMI. The analysis also underscores notable CNVs with an average gene copy number equal to or greater than four in , , , , , and genes. These findings provide further insight into the role of CNVs in VF in the context of STEAMI.

References

Saumarez R, Camm A, Panagos A, Gill J, Stewart J, de Belder M . Ventricular fibrillation in hypertrophic cardiomyopathy is associated with increased fractionation of paced right ventricular electrograms. Circulation. 1992; 86(2):467-74. DOI: 10.1161/01.cir.86.2.467. View

Benjamini Y, Speed T . Summarizing and correcting the GC content bias in high-throughput sequencing. Nucleic Acids Res. 2012; 40(10):e72. PMC: 3378858. DOI: 10.1093/nar/gks001. View

Huang Y, Huang X, Zeng J, Lin J . Knockdown of MUC16 (CA125) Enhances the Migration and Invasion of Hepatocellular Carcinoma Cells. Front Oncol. 2021; 11:667669. PMC: 8208084. DOI: 10.3389/fonc.2021.667669. View

Zee R, Ridker P, Chasman D . Genetic variants in eleven telomere-associated genes and the risk of incident cardio/cerebrovascular disease: The Women's Genome Health Study. Clin Chim Acta. 2010; 412(1-2):199-202. PMC: 3012433. DOI: 10.1016/j.cca.2010.10.003. View

Boeva V, Zinovyev A, Bleakley K, Vert J, Janoueix-Lerosey I, Delattre O . Control-free calling of copy number alterations in deep-sequencing data using GC-content normalization. Bioinformatics. 2010; 27(2):268-9. PMC: 3018818. DOI: 10.1093/bioinformatics/btq635. View

Stranger B, Forrest M, Dunning M, Ingle C, Beazley C, Thorne N . Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science. 2007; 315(5813):848-53. PMC: 2665772. DOI: 10.1126/science.1136678. View

Olshen A, Venkatraman E, Lucito R, Wigler M . Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics. 2004; 5(4):557-72. DOI: 10.1093/biostatistics/kxh008. View

Geng B, Cai Y, Gao S, Lu J, Zhang L, Zou J . PARP-2 knockdown protects cardiomyocytes from hypertrophy via activation of SIRT1. Biochem Biophys Res Commun. 2012; 430(3):944-50. DOI: 10.1016/j.bbrc.2012.11.132. View

Valla M, Opdahl S, Ytterhus B, Bofin A . DTX3 copy number increase in breast cancer: a study of associations to molecular subtype, proliferation and prognosis. Breast Cancer Res Treat. 2021; 187(1):57-67. PMC: 8062392. DOI: 10.1007/s10549-021-06138-2. View

10.

Keitges E, Pasion R, Burnside R, Mason C, Gonzalez-Ruiz A, Dunn T . Prenatal diagnosis of two fetuses with deletions of 8p23.1, critical region for congenital diaphragmatic hernia and heart defects. Am J Med Genet A. 2013; 161A(7):1755-8. DOI: 10.1002/ajmg.a.35965. View

11.

Zhong X, Chen Y, Long X, Chen H, Zheng Z, Pan H . Ultrasound-targeted microbubble destruction (UTMD)-mediated miR-150-5p attenuates oxygen and glucose deprivation-induced cardiomyocyte injury by inhibiting TTC5 expression. Mol Biol Rep. 2022; 49(7):6041-6052. DOI: 10.1007/s11033-022-07392-3. View

12.

McKeown P, Merlini P, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M . Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009; 41(3):334-41. PMC: 2681011. DOI: 10.1038/ng.327. View

13.

Wu H, Cao G, Wang Y, Tian H, Du R . Increased Serum CA125 and Brain-Derived Neurotrophic Factor (BDNF) Levels on Acute Myocardial Infarction: A Predictor for Acute Heart Failure. Med Sci Monit. 2019; 25:913-919. PMC: 6367886. DOI: 10.12659/MSM.912642. View

14.

Bentley R, Pearson J, Gearry R, Barclay M, McKinney C, Merriman T . Association of higher DEFB4 genomic copy number with Crohn's disease. Am J Gastroenterol. 2009; 105(2):354-9. DOI: 10.1038/ajg.2009.582. View

15.

Hundahl L, Tfelt-Hansen J, Jespersen T . Rat Models of Ventricular Fibrillation Following Acute Myocardial Infarction. J Cardiovasc Pharmacol Ther. 2017; 22(6):514-528. DOI: 10.1177/1074248417702894. View

16.

Zhao L, Liu H, Yuan X, Gao K, Duan J . Comparative study of whole exome sequencing-based copy number variation detection tools. BMC Bioinformatics. 2020; 21(1):97. PMC: 7059689. DOI: 10.1186/s12859-020-3421-1. View

17.

Brownstein C, Douard E, Haynes R, Koh H, Haghighi A, Keywan C . Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age. Adv Genet (Hoboken). 2023; 4(1):2200012. PMC: 10000288. DOI: 10.1002/ggn2.202200012. View

18.

Singer E, Ross S, Skinner J, Weintraub R, Ingles J, Semsarian C . Characterization of clinically relevant copy-number variants from exomes of patients with inherited heart disease and unexplained sudden cardiac death. Genet Med. 2020; 23(1):86-93. DOI: 10.1038/s41436-020-00970-5. View

19.

Demidova M, Smith J, Hoijer C, Holmqvist F, Erlinge D, Platonov P . Prognostic impact of early ventricular fibrillation in patients with ST-elevation myocardial infarction treated with primary PCI. Eur Heart J Acute Cardiovasc Care. 2013; 1(4):302-11. PMC: 3760561. DOI: 10.1177/2048872612463553. View

20.

Bofin A, Ytterhus B, Klaestad E, Valla M . copy number in breast cancer: associations with proliferation, histopathological grade and molecular subtypes. J Clin Pathol. 2021; 75(7):459-464. DOI: 10.1136/jclinpath-2021-207456. View