Decreased FAM13B Expression Increases Atrial Fibrillation Susceptibility by Regulating Sodium Current and Calcium Handling

被引：2

作者：

Tchou, Gregory ^{[1
,2
]}

Ponce-Balbuena, Daniela ^{[3
]}

Liu, Nana ^{[1
,2
,7
]}

Gore-Panter, Shamone ^{[1
,2
]}

Hsu, Jeffrey ^{[1
,2
,6
]}

Liu, Fang ^{[1
,2
]}

Opoku, Emmanuel ^{[1
,2
]}

Brubaker, Gregory ^{[1
,2
]}

Schumacher, Sarah M. ^{[1
,2
]}

Moravec, Christine S. ^{[1
,2
,4
]}

Barnard, John ^{[5
]}

Van Wagoner, David R. ^{[1
,2
,4
]}

Chung, Mina K. ^{[1
,2
,4
,8
]}

Smith, Jonathan D. ^{[1
,2
,8
]}

机构：

[1] Cleveland Clin, Dept Cardiovasc, Cleveland, OH USA

[2] Cleveland Clin, Dept Metab Sci, Cleveland, OH USA

[3] Ohio State Univ, Dept Physiol & Cell Biol, Columbus, OH USA

[4] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH USA

[5] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA

[6] Ivy Natal, San Francisco, CA USA

[7] Guilin Med Univ, Guilin, Guangxi, Peoples R China

[8] Cleveland Clin, Cardiovasc & Metab Sci, Box ND50,9500 Euclid Ave, Cleveland, OH 44195 USA

来源：

JACC-BASIC TO TRANSLATIONAL SCIENCE | 2023年 / 8卷 / 10期

基金：

美国国家卫生研究院;

关键词：

KEY WORDS CRISPR gene editing; functional genomics; pacing-induced arrhythmia; Rho GTPase-activating protein; QT INTERVAL; ASSOCIATION; RISK; CLONING; GENE;

D O I：

10.1016/j.jacbts.2023.05.009

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

A specific genetic variant associated with atrial fibrillation risk, rs17171731, was identified as a regulatory variant responsible for controlling FAM13B expression. The atrial fibrillation risk allele decreases FAM13B expression, whose knockdown alters the expression of many genes in stem cell-derived cardiomyocytes, including SCN2B, and led to pro-arrhythmogenic changes in the late sodium current and Ca2 thorn cycling. Fam13b knockout mice increased P-wave and QT interval duration and were more susceptible to pacing-induced arrhythmias vs control mice. FAM13B expression, its regulation, and downstream effects are potential targets for investigation of patient-specific therapeutics. (J Am Coll Cardiol Basic Trans Science 2023;8:1357-1378) (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：1357 / 1378

页数：22

共 52 条

[1] Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization [J].

Arking, Dan E. ;

Pulit, Sara L. ;

Crotti, Lia ;

Van der Harst, Pim ;

Munroe, Patricia B. ;

Koopmann, Tamara T. ;

Sotoodehnia, Nona ;

Rossin, Elizabeth J. ;

Morley, Michael ;

Wang, Xinchen ;

Johnson, Andrew D. ;

Lundby, Alicia ;

Gudbjartsson, Daniel F. ;

Noseworthy, Peter A. ;

Eijgelsheim, Mark ;

Bradford, Yuki ;

Tarasov, Kirill V. ;

Dorr, Marcus ;

Miiller-Nurasyid, Martina ;

Lahtinen, Annukka M. ;

Nolte, Ilja M. ;

Smith, Albert Vernon ;

Bis, Joshua C. ;

Isaacs, Aaron ;

Newhouse, Stephen J. ;

Evans, Daniel S. ;

Post, Wendy S. ;

Waggott, Daryl ;

Lyytikainen, Leo-Pekka ;

Hicks, Andrew A. ;

Eisele, Lewin ;

Ellinghaus, David ;

Hayward, Caroline ;

Navarro, Pau ;

Ulivi, Sheila ;

Tanaka, Toshiko ;

Tester, David J. ;

Chatel, Stephanie ;

Gustafsson, Stefan ;

Kumari, Meena ;

Morris, Richard W. ;

Naluai, Asa T. ;

Padmanabhan, Sandosh ;

Kluttig, Alexander ;

Strohmer, Bernhard ;

Panayiotou, Andrie G. ;

Torres, Maria ;

Knoflach, Michael ;

Hubacek, Jaroslav A. ;

Slowikowski, Kamil .

NATURE GENETICS, 2014, 46 (08) :826-836

[2] Scn2b Deletion in Mice Results in Ventricular and Atrial Arrhythmias [J].

Bao, Yangyang ;

Willis, B. Cicero ;

Frasier, Chad R. ;

Lopez-Santiago, Luis F. ;

Lin, Xianming ;

Ramos-Mondragon, Roberto ;

Auerbach, David S. ;

Chen, Chunling ;

Wang, Zhenxun ;

Anumonwo, Justus ;

Valdivia, Hector H. ;

Delmar, Mario ;

Jalife, Jose ;

Isom, Lori L. .

CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, 2016, 9 (12)

[3] Knock-in gain-of-function sodium channel mutation prolongs atrial action potentials and alters atrial vulnerability [J].

Blana, Andreas ;

Kaese, Sven ;

Fortmueller, Lisa ;

Laakmann, Sandra ;

Damke, Dierk ;

van Bragt, Kelly ;

Eckstein, Jens ;

Piccini, Ilaria ;

Kirchhefer, Uwe ;

Nattel, Stanley ;

Breithardt, Guenter ;

Carmeliet, Peter ;

Carmeliet, Edward ;

Schotten, Ulrich ;

Verheule, Sander ;

Kirchhof, Paulus ;

Fabritz, Larissa .

HEART RHYTHM, 2010, 7 (12) :1862-1869

[4]

ccf, Human LAA eQTL data

[5] Monogenic and Polygenic Contributions to Atrial Fibrillation Risk Results From a National Biobank [J].

Choi, Seung Hoan ;

Jurgens, Sean J. ;

Weng, Lu-Chen ;

Pirruccello, James P. ;

Roselli, Carolina ;

Chaffin, Mark ;

Lee, Christina J. -Y. ;

Hall, Amelia W. ;

Khera, Amit V. ;

Lunetta, Kathryn L. ;

Lubitz, Steven A. ;

Ellinor, Patrick T. .

CIRCULATION RESEARCH, 2020, 126 (02) :200-209

[6] Cloning and characterization of FAM13A1 -: a gene near a milk protein QTL on BTA6:: evidence for population-wide linkage disequilibrium in Israeli Holsteins [J].

Cohen, M ;

Reichenstein, M ;

Everts-van der Wind, A ;

Heon-Lee, J ;

Shani, M ;

Lewin, HA ;

Weller, JI ;

Ron, M ;

Seroussi, E .

GENOMICS, 2004, 84 (02) :374-383

[7] Inference of CRISPR Edits from Sanger Trace Data [J].

Conant, David ;

Hsiau, Tim ;

Rossi, Nicholas ;

Oki, Jennifer ;

Maures, Travis ;

Waite, Kelsey ;

Yang, Joyce ;

Joshi, Sahil ;

Kelso, Reed ;

Holden, Kevin ;

Enzmann, Brittany L. ;

Stoner, Rich .

CRISPR JOURNAL, 2022, 5 (01) :123-130

[8] Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation [J].

Darbar, Dawood ;

Kannankeril, Prince J. ;

Donahue, Brian S. ;

Kucera, Gayle ;

Stubblefield, Tanya ;

Haines, Jonathan L. ;

George, Alfred L., Jr. ;

Roden, Dan M. .

CIRCULATION, 2008, 117 (15) :1927-1935

[9] Phospho-ablation of cardiac sodium channel Nav1.5 mitigates susceptibility to atrial fibrillation and improves glucose homeostasis under conditions of diet-induced obesity [J].

Dewal, Revati S. ;

Greer-Short, Amara ;

Lane, Cemantha ;

Nirengi, Shinsuke ;

Manzano, Pedro Acosta ;

Hernandez-Saavedra, Diego ;

Wright, Katherine R. ;

Nassal, Drew ;

Baer, Lisa A. ;

Mohler, Peter J. ;

Hund, Thomas J. ;

Stanford, Kristin I. .

INTERNATIONAL JOURNAL OF OBESITY, 2021, 45 (04) :795-807

[10] Familial aggregation in lone atrial fibrillation [J].

Ellinor, PT ;

Yoerger, DM ;

Ruskin, JN ;

MacRae, CA .

HUMAN GENETICS, 2005, 118 (02) :179-184

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