Genetics of Atrial Fibrilation: In Search of Novel Therapeutic Targets

Author(s): Estefanía Lozano-Velasco, Carlos Garcia-Padilla, Amelia E. Aránega, Diego Franco*

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets
Formerly Current Drug Targets - Cardiovascular & Hematological Disorders

Volume 19 , Issue 3 , 2019

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Graphical Abstract:


Atrial fibrillation (AF) is the most frequent arrhythmogenic disease in humans, ranging from 2% in the general population and rising up to 10-12% in 80+ years. Genetic analyses of AF familiar cases have identified a series of point mutations in distinct ion channels, supporting a causative link. However, these genetic defects only explain a minority of AF patients. Genomewide association studies identified single nucleotide polymorphisms (SNPs), close to PITX2 on 4q25 chromosome, that are highly associated to AF. Subsequent GWAS studies have identified several new loci, involving additional transcription and growth factors. Furthermore, these risk 4q25 SNPs serve as surrogate biomarkers to identify AF recurrence in distinct surgical and pharmacological interventions. Experimental studies have demonstrated an intricate signalling pathway supporting a key role of the homeobox transcription factor PITX2 as a transcriptional regulator. Furthermore, cardiovascular risk factors such as hyperthyroidism, hypertension and redox homeostasis have been identified to modulate PITX2 driven gene regulatory networks. We provide herein a state-of-the-art review of the genetic bases of atrial fibrillation, our current understanding of the genetic regulatory networks involved in AF and its plausible usage for searching novel therapeutic targets.

Keywords: Atrial fibrillation, PITX2, non-coding RNAs, SNPs, hyperthyroidism, hypertension.

Hakim, F.A.; Shen, W.K. Atrial fibrillation in the elderly: A review. Future Cardiol., 2014, 10, 745-758.
Abed, H.S.; Wittert, G.A. Obesity and atrial fibrillation. Obes. Rev., 2013, 14, 929-938.
Vargas-Uricoechea, H.; Sierra-Torres, C.H. Thyroid hormones and the heart. Horm. Mol. Biol. Clin. Investig., 2014, 18, 15-26.
Goudis, C.A.; Korantzopoulos, P.; Ntalas, I.V.; Kallergis, E.M.; Liu, T.; Ketikoglou, D.G. Diabetes mellitus and atrial fibrillation: Pathophysiological mechanisms and potential upstream therapies. Int. J. Cardiol., 2015, 184, 617-622.
De Caterina, R.; Camm, A.J. What is ‘valvular’ atrial fibrillation? A reappraisal. Eur. Heart J., 2014, 35, 3328-3335.
Kumar, K.R.; Mandleywala, S.N.; Link, M.S. Atrial and ventricular arrhythmias in hypertrophic cardiomyopathy. Card. Electrophysiol. Clin., 2015, 7, 173-186.
Riber, L.P.; Larsen, T.B.; Christensen, T.D. Postoperative atrial fibrillation prophylaxis after lung surgery: systematic review and meta-analysis. Ann. Thorac. Surg., 2014, 98, 1989-1997.
Qaddoura, A.; Kabali, C.; Drew, D.; van Oosten, E.M.; Michael, K.A.; Redfearn, D.P.; Simpson, C.S.; Baranchuk, A. Obstructive sleep apnea as a predictor of atrial fibrillation after coronary artery bypass grafting: A systematic review and meta-analysis. Can. J. Cardiol., 2014, 30, 1516-2522.
Anumonwo, J.M.; Kalifa, J. Risk factors and genetics of atrial fibrillation. Cardiol. Clin., 2014, 32, 485-494.
Yadava, M.; Hughey, A.B.; Crawford, T.C. Postoperative atrial fibrillation: Incidence, mechanisms, and clinical correlates. Cardiol. Clin., 2014, 32, 627-636.
Akoum, N.; Marrouche, N. Assessment and impact of cardiac fibrosis on atrial fibrillation. Curr. Cardiol. Rep., 2014, 16, 518.
Berenfeld, O.; Jalife, J. Mechanisms of atrial fibrillation: rotors, ionic determinants, and excitation frequency. Cardiol. Clin., 2014, 32, 495-506.
Heijman, J.; Voigt, N.; Wehrens, X.H.; Dobrev, D. Calcium dysregulation in atrial fibrillation: the role of CaMKII. Front. Pharmacol., 2014, 5, 30.
Wolke, C.; Bukowska, A.; Goette, A.; Lendeckel, U. Redox control of cardiac remodeling in atrial fibrillation. Biochim. Biophys. Acta, 2015, 1850, 1555-1565.
Jalife, J.; Kaur, K. Atrial remodeling, fibrosis, and atrial fibrillation. Trends Cardiovasc. Med., 2015, 25, 475-484.
Corradi, D. Atrial fibrillation from the pathologist’s perspective. Cardiovasc. Pathol., 2014, 23, 71-84.
Seno, K.; Lane, D.; Lip, G.Y. Stroke and bleeding risk in atrial fibrillation. Korean Circ. J., 2014, 44, 281-290.
Zimetbaum, P.; Waks, J.W.; Ellis, E.R.; Glotzer, T.V.; Passman, R.S. Role of atrial fibrillation burden in assessing thromboembolic risk. Circ Arrhythm Electrophysiol, 2014, 7, 1223-1229.
Hirsh, B.J.; Copeland-Halperin, R.S.; Halperin, J.L. Fibrotic atrial cardiomyopathy, atrial fibrillation, and thromboembolism: Mechanistic links and clinical inferences. J. Am. Coll. Cardiol., 2015, 65, 2239-2251.
Hui, D.S.; Morley, J.E.; Mikolajczak, P.C.; Lee, R. Atrial fibrillation: A major risk factor for cognitive decline. Am. Heart J., 2015, 169, 448-456.
Jacobs, V.; Cutler, M.J.; Day, J.D.; Bunch, T.J. Atrial fibrillation and dementia. Trends Cardiovasc. Med., 2015, 25, 44-51.
Luong, C.; Barnes, M.E.; Tsang, T.S. Atrial fibrillation and heart failure: cause or effect? Curr. Heart Fail. Rep., 2014, 11, 463-470.
Wijesurendra, R.S.; Casadei, B. Atrial fibrillation: effects beyond the atrium? Cardiovasc. Res., 2015, 105, 238-247.
Chen, L.Y.; Benditt, D.G.; Alonso, A. Atrial fibrillation and its association with sudden cardiac death. Circ. J., 2014, 78, 2588-2593.
Potpara, T.S.; Lip, G.Y. A brief history of ‘lone’ atrial fibrillation: from ‘a peculiar pulse irregularity’ to a modern public health concern. Curr. Pharm. Des., 2015, 21, 679-696.
Tello-Montoliu, A.; Hernández-Romero, D.; Sanchez-Martínez, M.; Valdes, M.; Marín, F. Lone atrial fibrillation - a diagnosis of exclusion. Curr. Pharm. Des., 2015, 21, 544-550.
Brugada, R.; Tapscott, T.; Czernuszewicz, G.Z.; Marian, A.J.; Iglesias, A.; Mont, L.; Brugada, J.; Girona, J.; Domingo, A.; Bachinski, L.L.; Roberts, R. Identification of a genetic locus for familial atrial fibrillation. N. Engl. J. Med., 1997, 336, 905-911.
Chen, Y.H.; Xu, S.J.; Bendahhou, S.; Wang, X.L.; Wang, Y.; Xu, W.Y.; Jin, H.W.; Sun, H.; Su, X.Y.; Zhuang, Q.N.; Yang, Y.Q.; Li, Y.B.; Liu, Y.; Xu, H.J.; Li, X.F.; Ma, N.; Mou, C.P.; Chen, Z.; Barhanin, J.; Huang, W. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science, 2003, 299, 251-254.
Xia, M.; Jin, Q.; Bendahhou, S.; He, Y.; Larroque, M.M.; Chen, Y.; Zhou, Q.; Yang, Y.; Liu, Y.; Liu, B.; Zhu, Q.; Zhou, Y.; Lin, J.; Liang, B.; Li, L.; Dong, X.; Pan, Z.; Wang, R.; Wan, H.; Qiu, W.; Xu, W.; Eurlings, P.; Barhanin, J.; Chen, Y.A. Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochem. Biophys. Res. Commun., 2005, 332, 1012-1019.
Yang, Y.; Xia, M.; Jin, Q.; Bendahhou, S.; Shi, J.; Chen, Y.; Liang, B.; Lin, J.; Liu, Y.; Liu, B.; Zhou, Q.; Zhang, D.; Wang, R.; Ma, N.; Su, X.; Niu, K.; Pei, Y.; Xu, W.; Chen, Z.; Wan, H.; Cui, J.; Barhanin, J.; Chen, Y. Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am. J. Hum. Genet., 2004, 75, 899-905.
Berenfeld, O.; Zaitsev, A.V.; Mironov, S.F.; Pertsov, A.M.; Jalife, J. Frequency-dependent breakdown of wave propagation into fibrillatory conduction across the pectinate muscle network in the isolated sheep right atrium. Circ. Res., 2002, 90, 1173-1180.
Chen, J.; Mandapati, R.; Berenfeld, O.; Skanes, A.C.; Gray, R.A.; Jalife, J. Dynamics of wavelets and their role in atrial fibrillation in the isolated sheep heart. Cardiovasc. Res., 2000, 48, 220-232.
Mandapati, R.; Skanes, A.; Chen, J.; Berenfeld, O.; Jalife, J. Stable microreentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. Circulation, 2000, 101, 194-199.
Gudbjartsson, D.F.; Arnar, D.O.; Helgadottir, A.; Gretarsdottir, S.; Holm, H.; Sigurdsson, A.; Jonasdottir, A.; Baker, A.; Thorleifsson, G.; Kristjansson, K.; Palsson, A.; Blondal, T.; Sulem, P.; Backman, V.M.; Hardarson, G.A.; Palsdottir, E.; Helgason, A.; Sigurjonsdottir, R.; Sverrisson, J.T.; Kostulas, K.; Ng, M.C.; Baum, L.; So, W.Y.; Wong, K.S.; Chan, J.C.; Furie, K.L.; Greenberg, S.M.; Sale, M.; Kelly, P.; MacRae, C.A.; Smith, E.E.; Rosand, J.; Hillert, J.; Ma, R.C.; Ellinor, P.T.; Thorgeirsson, G.; Gulcher, J.R.; Kong, A.; Thorsteinsdottir, U.; Stefansson, K. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature, 2007, 448, 353-357.
Benjamin, E.J.; Rice, K.M.; Arking, D.E.; Pfeufer, A.; van Noord, C.; Smith, A.V.; Schnabel, R.B.; Bis, J.C.; Boerwinkle, E.; Sinner, M.F.; Dehghan, A.; Lubitz, S.A.; D’Agostino, R.B. Sr, Lumley, T.; Ehret, G.B.; Heeringa, J.; Aspelund, T.; Newton-Cheh, C.; Larson, M.G.; Marciante, K.D.; Soliman, E.Z.; Rivadeneira, F.; Wang, T.J.; Eiríksdottir, G.; Levy, D.; Psaty, B.M.; Li, M.; Chamberlain, A.M.; Hofman, A.; Vasan, R.S.; Harris, T.B.; Rotter, J.I.; Kao, W.H.; Agarwal, S.K.; Stricker, B.H.; Wang, K.; Launer, L.J.; Smith, N.L.; Chakravarti, A.; Uitterlinden, A.G.; Wolf, P.A.; Sotoodehnia, N.; Köttgen, A.; van Duijn, C.M.; Meitinger, T.; Mueller, M.; Perz, S.; Steinbeck, G.; Wichmann, H.E.; Lunetta, K.L.; Heckbert, S.R.; Gudnason, V.; Alonso, A.; Kääb, S.; Ellinor, P.T.; Witteman, J.C. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat. Genet., 2009, 41, 879-881.
Ellinor, P.T.; Lunetta, K.L.; Albert, C.M.; Glazer, N.L.; Ritchie, M.D.; Smith, A.V.; Arking, D.E.; Müller-Nurasyid, M.; Krijthe, B.P.; Lubitz, S.A.; Bis, J.C.; Chung, M.K.; Dörr, M.; Ozaki, K.; Roberts, J.D.; Smith, J.G.; Pfeufer, A.; Sinner, M.F.; Lohman, K.; Ding, J.; Smith, N.L.; Smith, J.D.; Rienstra, M.; Rice, K.M.; Van Wagoner, D.R.; Magnani, J.W.; Wakili, R.; Clauss, S.; Rotter, J.I.; Steinbeck, G.; Launer, L.J.; Davies, R.W.; Borkovich, M.; Harris, T.B.; Lin, H.; Völker, U.; Völzke, H.; Milan, D.J.; Hofman, A.; Boerwinkle, E.; Chen, L.Y.; Soliman, E.Z.; Voight, B.F.; Li, G.; Chakravarti, A.; Kubo, M.; Tedrow, U.B.; Rose, L.M.; Ridker, P.M.; Conen, D.; Tsunoda, T.; Furukawa, T.; Sotoodehnia, N.; Xu, S.; Kamatani, N.; Levy, D.; Nakamura, Y.; Parvez, B.; Mahida, S.; Furie, K.L.; Rosand, J.; Muhammad, R.; Psaty, B.M.; Meitinger, T.; Perz, S.; Wichmann, H.E.; Witteman, J.C.; Kao, W.H.; Kathiresan, S.; Roden, D.M.; Uitterlinden, A.G.; Rivadeneira, F.; McKnight, B.; Sjögren, M.; Newman, A.B.; Liu, Y.; Gollob, M.H.; Melander, O.; Tanaka, T.; Stricker, B.H.; Felix, S.B.; Alonso, A.; Darbar, D.; Barnard, J.; Chasman, D.I.; Heckbert, S.R.; Benjamin, E.J.; Gudnason, V.; Kääb, S. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat. Genet., 2012, 44, 670-675.
Ellinor, P.T.; Lunetta, K.L.; Glazer, N.L.; Pfeufer, A.; Alonso, A.; Chung, M.K.; Sinner, M.F.; de Bakker, P.I.; Mueller, M.; Lubitz, S.A.; Fox, E.; Darbar, D.; Smith, N.L.; Smith, J.D.; Schnabel, R.B.; Soliman, E.Z.; Rice, K.M.; Van Wagoner, D.R.; Beckmann, B.M.; van Noord, C.; Wang, K.; Ehret, G.B.; Rotter, J.I.; Hazen, S.L.; Steinbeck, G.; Smith, A.V.; Launer, L.J.; Harris, T.B.; Makino, S.; Nelis, M.; Milan, D.J.; Perz, S.; Esko, T.; Köttgen, A.; Moebus, S.; Newton-Cheh, C.; Li, M.; Möhlenkamp, S.; Wang, T.J.; Kao, W.H.; Vasan, R.S.; Nöthen, M.M.; MacRae, C.A.; Stricker, B.H.; Hofman, A.; Uitterlinden, A.G.; Levy, D.; Boerwinkle, E.; Metspalu, A.; Topol, E.J.; Chakravarti, A.; Gudnason, V.; Psaty, B.M.; Roden, D.M.; Meitinger, T.; Wichmann, H.E.; Witteman, J.C.; Barnard, J.; Arking, D.E.; Benjamin, E.J.; Heckbert, S.R.; Kääb, S. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat. Genet., 2010, 42, 240-244.
Gudbjartsson, D.F.; Holm, H.; Gretarsdottir, S.; Thorleifsson, G.; Walters, G.B.; Thorgeirsson, G.; Gulcher, J.; Mathiesen, E.B.; Njølstad, I.; Nyrnes, A.; Wilsgaard, T.; Hald, E.M.; Hveem, K.; Stoltenberg, C.; Kucera, G.; Stubblefield, T.; Carter, S.; Roden, D.; Ng, M.C.; Baum, L.; So, W.Y.; Wong, K.S.; Chan, J.C.; Gieger, C.; Wichmann, H.E.; Gschwendtner, A.; Dichgans, M.; Kuhlenbäumer, G.; Berger, K.; Ringelstein, E.B.; Bevan, S.; Markus, H.S.; Kostulas, K.; Hillert, J.; Sveinbjörnsdóttir, S.; Valdimarsson, E.M.; Løchen, M.L.; Ma, R.C.; Darbar, D.; Kong, A.; Arnar, D.O.; Thorsteinsdottir, U.; Stefansson, K. A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat. Genet., 2009, 41, 876-878.
Schnabel, R.B.; Kerr, K.F.; Lubitz, S.A.; Alkylbekova, E.L.; Marcus, G.M.; Sinner, M.F.; Magnani, J.W.; Wolf, P.A.; Deo, R.; Lloyd-Jones, D.M.; Lunetta, K.L.; Mehra, R.; Levy, D.; Fox, E.R.; Arking, D.E.; Mosley, T.H.; Müller-Nurasyid, M.; Young, T.R.; Wichmann, H.E.; Seshadri, S.; Farlow, D.N.; Rotter, J.I.; Soliman, E.Z.; Glazer, N.L.; Wilson, J.G.; Breteler, M.M.; Sotoodehnia, N.; Newton-Cheh, C.; Kääb, S.; Ellinor, P.T.; Alonso, A.; Benjamin, E.J.; Heckbert, S.R. Candidate Gene Association Resource. (CARe) Atrial Fibrillation/Electrocardiography Working Group. Large-scale candidate gene analysis in whites and African Americans identifies IL6R polymorphism in relation to atrial fibrillation: the National Heart, Lung, and Blood Institute’s Candidate Gene Association Resource (CARe) project. Circ Cardiovasc Genet, 2011, 4, 557-564.
He, J.; Zhu, W.; Yu, Y.; Hu, J.; Hong, K. Variant rs2200733 and rs10033464 on chromosome 4q25 are associated with increased risk of atrial fibrillation after catheter ablation: Evidence from a meta-analysis. Cardiol. J., 2018, 25(5), 628-638.
Miyazaki, S.; Ebana, Y.; Liu, L.; Nakamura, H.; Hachiya, H.; Taniguchi, H.; Takagi, T.; Kajiyama, T.; Watanabe, T.; Igarashi, M.; Kusa, S.; Niida, T.; Iesaka, Y.; Furukawa, T. Chromosome 4q25 variants and recurrence after second-generation cryoballoon ablation in patients with paroxysmal atrial fibrillation. Int. J. Cardiol., 2017, 244, 151-157.
Zhao, L.Q.; Zhang, G.B.; Wen, Z.J.; Huang, C.K.; Wu, H.Q.; Xu, J.; Qi, B.Z.; Wang, Z.M.; Shi, Y.Y.; Liu, S.W. Common variants predict recurrence after nonfamilial atrial fibrillation ablation in Chinese Han population. Int. J. Cardiol., 2017, 227, 360-366.
Chen, F.; Yang, Y.; Zhang, R.; Zhang, S.; Dong, Y.; Yin, X.; Chang, D.; Yang, Z.; Wang, K.; Gao, L.; Xia, Y. Polymorphism rs2200733 at chromosome 4q25 is associated with atrial fibrillation recurrence after radiofrequency catheter ablation in the Chinese Han population. Am. J. Transl. Res., 2016, 8, 688-697.
Parvez, B.; Shoemaker, M.B.; Muhammad, R.; Richardson, R.; Jiang, L.; Blair, M.A.; Roden, D.M.; Darbar, D. Common genetic polymorphism at 4q25 locus predicts atrial fibrillation recurrence after successful cardioversion. Heart Rhythm, 2013, 10, 849-855.
Benjamin Shoemaker, M.; Muhammad, R.; Parvez, B.; White, B.W.; Streur, M.; Song, Y.; Stubblefield, T.; Kucera, G.; Blair, M.; Rytlewski, J.; Parvathaneni, S.; Nagarakanti, R.; Saavedra, P.; Ellis, C.R.; Patrick Whalen, S.; Roden, D.M.; Darbar, R.D. Common atrial fibrillation risk alleles at 4q25 predict recurrence after catheter-based atrial fibrillation ablation. Heart Rhythm, 2013, 10, 394-400.
Husser, D.; Adams, V.; Piorkowski, C.; Hindricks, G.; Bollmann, A. Chromosome 4q25 variants and atrial fibrillation recurrence after catheter ablation. J. Am. Coll. Cardiol., 2010, 55(8), 747-753.
Amin, A.S.; Bhuiyan, Z.A. SCN5A mutations in atrial fibrillation. Heart Rhythm, 2010, 7, 1870-1871.
Blana, A.; Kaese, S.; Fortmüller, L.; Laakmann, S.; Damke, D.; van Bragt, K.; Eckstein, J.; Piccini, I.; Kirchhefer, U.; Nattel, S.; Breithardt, G.; Carmeliet, P.; Carmeliet, E.; Schotten, U.; Verheule, S.; Kirchhof, P.; Fabritz, L. Knock-in gain-of-function sodium channel mutation prolongs atrial action potentials and alters atrial vulnerability. Heart Rhythm, 2010, 7, 1862-1869.
Laitinen-Forsblom, P.J.; Mäkynen, P.; Mäkynen, H.; Yli-Mäyry, S.; Virtanen, V.; Kontula, K.; Aalto-Setälä, K. SCN5A mutation associated with cardiac conduction defect and atrial arrhythmias. J. Cardiovasc. Electrophysiol., 2006, 17, 480-485.
Li, Q.; Huang, H.; Liu, G.; Lam, K.; Rutberg, J.; Green, M.S.; Birnie, D.H.; Lemery, R.; Chahine, M.; Gollob, M.H. Gain-of-function mutation of Nav1.5 in atrial fibrillation enhances cellular excitability and lowers the threshold for action potential firing. Biochem. Biophys. Res. Commun., 2009, 380, 132-137.
Makiyama, T.; Akao, M.; Shizuta, S.; Doi, T.; Nishiyama, K.; Oka, Y. A novel SCN5A gain-of-function mutation M1875T associated with familial atrial fibrillation. J. Am. Coll. Cardiol., 2008, 52, 1326-1334.
Benito, B.; Brugada, R.; Perich, R.M.; Lizotte, E.; Cinca, J.; Mont, L.; Berruezo, A.; Tolosana, J.M.; Freixa, X.; Brugada, P.; Brugada, J. A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation. Heart Rhythm, 2008, 5, 1434-1440.
Calloe, K.; Schmitt, N.; Grubb, S.; Pfeiffer, R.; David, J.P.; Kanter, R.; Cordeiro, J.M.; Antzelevitch, C. Multiple arrhythmic syndromes in a newborn, owing to a novel mutation in SCN5A. Can. J. Physiol. Pharmacol., 2011, 89, 723-736.
Dolz-Gaitón, P.; Núñez, M.; Núñez, L.; Barana, A.; Amorós, I.; Matamoros, M.; Pérez-Hernández, M.; González de la Fuente, M.; Alvarez-López, M.; Macías-Ruiz, R.; Tercedor-Sánchez, L.; Jiménez-Jáimez, J.; Delpón, E.; Caballero, R.; Tamargo, J. Functional characterization of a novel frameshift mutation in the C-terminus of the Nav1.5 channel underlying a Brugada syndrome with variable expression in a Spanish family. PLoS One, 2013, 8e81493
Olson, T.M.; Michels, V.V.; Ballew, J.D.; Reyna, S.P.; Karst, M.L.; Herron, K.J.; Horton, S.C.; Rodeheffer, R.J.; Anderson, J.L. Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA, 2005, 293, 447-454.
Ziyadeh-Isleem, A.; Clatot, J.; Duchatelet, S.; Gandjbakhch, E.; Denjoy, I.; Hidden-Lucet, F.; Hatem, S.; Deschênes, I.; Coulombe, A.; Neyroud, N.; Guicheney, P. A truncating SCN5A mutation combined with genetic variability causes sick sinus syndrome and early atrial fibrillation. Heart Rhythm, 2014, 11, 1015-1023.
Rossenbacker, T.; Carroll, S.J.; Liu, H.; Kuipéri, C.; de Ravel, T.J.; Devriendt, K.; Carmeliet, P.; Kass, R.S.; Heidbüchel, H. Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death. Heart Rhythm, 2004, 1, 610-615.
Watanabe, H.; Darbar, D.; Kaiser, D.W.; Jiramongkolchai, K.; Chopra, S.; Donahue, B.S.; Kannankeril, P.J.; Roden, D.M. Mutations in sodium channel β1- and β2-subunits associated with atrial fibrillation. Circ Arrhythm Electrophysiol, 2009, 2, 268-275.
Wang, P.; Yang, Q.; Wu, X.; Yang, Y.; Shi, L.; Wang, C.; Wu, G.; Xia, Y.; Yang, B.; Zhang, R.; Xu, C.; Cheng, X.; Li, S.; Zhao, Y.; Fu, F.; Liao, Y.; Fang, F.; Chen, Q.; Tu, X.; Wang, Q.K. Functional dominant-negative mutation of sodium channel subunit gene SCN3B associated with atrial fibrillation in a Chinese GeneID population. Biochem. Biophys. Res. Commun., 2010, 398, 98-104.
Olesen, M.S.; Jespersen, T.; Nielsen, J.B.; Liang, B.; Møller, D.V.; Hedley, P.; Christiansen, M.; Varró, A.; Olesen, S.P.; Haunsø, S.; Schmitt, N.; Svendsen, J.H. Mutations in sodium channel β-subunit SCN3B are associated with early-onset lone atrial fibrillation. Cardiovasc. Res., 2011, 89, 786-793.
Li, R.G.; Wang, Q.; Xu, Y.J.; Zhang, M.; Qu, X.K.; Liu, X.; Fang, W.Y.; Yang, Y.Q. Mutations of the SCN4B-encoded sodium channel β4 subunit in familial atrial fibrillation. Int. J. Mol. Med., 2013, 32, 144-150.
Olesen, M.S.; Holst, A.G.; Svendsen, J.H.; Haunsø, S.; Tfelt-Hansen, J. SCN1Bb R214Q found in 3 patients: 1 with Brugada syndrome and 2 with lone atrial fibrillation. Heart Rhythm, 2012, 9, 770-773.
Macri, V.; Mahida, S.N.; Zhang, M.L.; Sinner, M.F.; Dolmatova, E.V.; Tucker, N.R.; McLellan, M.; Shea, M.A.; Milan, D.J.; Lunetta, K.L.; Benjamin, E.J.; Ellinor, P.T. A novel trafficking-defective HCN4 mutation is associated with early-onset atrial fibrillation. Heart Rhythm, 2014, 11, 1055-1062.
Hong, K.; Piper, D.R.; Diaz-Valdecantos, A.; Brugada, J.; Oliva, A.; Burashnikov, E.; Santos-de-Soto, J.; Grueso-Montero, J.; Diaz-Enfante, E.; Brugada, P.; Sachse, F.; Sanguinetti, M.C.; Brugada, R. De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovasc. Res., 2005, 68, 433-440.
Lundby, A.; Ravn, L.S.; Svendsen, J.H.; Olesen, S.P.; Schmitt, N. KCNQ1 mutation Q147R is associated with atrial fibrillation and prolonged QT interval. Heart Rhythm, 2007, 4, 1532-1541.
Kharche, S.; Adeniran, I.; Stott, J.; Law, P.; Boyett, M.R.; Hancox, J.C.; Zhang, H. Pro-arrhythmogenic effects of the S140G KCNQ1 mutation in human atrial fibrillation - insights from modelling. J. Physiol., 2012, 590, 4501-4514.
Das, S.; Makino, S.; Melman, Y.F.; Shea, M.A.; Goyal, S.B.; Rosenzweig, A.; Macrae, C.A.; Ellinor, P.T. Mutation in the S3 segment of KCNQ1 results in familial lone atrial fibrillation. Heart Rhythm, 2009, 6, 1146-1153.
El Harchi, A.; Zhang, H.; Hancox, J.C. The S140G KCNQ1 atrial fibrillation mutation affects ‘I(KS)’ profile during both atrial and ventricular action potentials. J. Physiol. Pharmacol., 2010, 61, 759-764.
Ravn, L.S.; Aizawa, Y.; Pollevick, G.D.; Hofman-Bang, J.; Cordeiro, J.M.; Dixen, U.; Jensen, G.; Wu, Y.; Burashnikov, E.; Haunso, S.; Guerchicoff, A.; Hu, D.; Svendsen, J.H.; Christiansen, M.; Antzelevitch, C. Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation. Heart Rhythm, 2008, 5, 427-435.
Nielsen, J.B.; Bentzen, B.H.; Olesen, M.S.; David, J.P.; Olesen, S.P.; Haunsø, S.; Svendsen, J.H.; Schmitt, N. Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation. Biomarkers Med., 2014, 8, 557-570.
Deo, M.; Ruan, Y.; Pandit, S.V.; Shah, K.; Berenfeld, O.; Blaufox, A.; Cerrone, M.; Noujaim, S.F.; Denegri, M.; Jalife, J.; Priori, S.G. KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia. Proc. Natl. Acad. Sci. USA, 2013, 110, 4291-4296.
Kharche, S.; Garratt, C.J.; Boyett, M.R.; Inada, S.; Holden, A.V.; Hancox, J.C.; Zhang, H. Atrial proarrhythmia due to increased inward rectifier current (I(K1)) arising from KCNJ2 mutation--a simulation study. Prog. Biophys. Mol. Biol., 2008, 98, 186-197.
Chelu, M.G.; Sarma, S.; Sood, S.; Wang, S.; van Oort, R.J.; Skapura, D.G.; Li, N.; Santonastasi, M.; Müller, F.U.; Schmitz, W.; Schotten, U.; Anderson, M.E.; Valderrábano, M.; Dobrev, D.; Wehrens, X.H. Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice. J. Clin. Invest., 2009, 119, 1940-1951.
Shan, J.; Xie, W.; Betzenhauser, M.; Reiken, S.; Chen, B.X.; Wronska, A.; Marks, A.R. Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia. Circ. Res., 2012, 111, 708-717.
Li, N.; Wang, T.; Wang, W.; Cutler, M.J.; Wang, Q.; Voigt, N.; Rosenbaum, D.S.; Dobrev, D.; Wehrens, X.H. Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial fibrillation in FKBP12.6 knockout mice. Circ. Res., 2012, 110, 465-470.
Di Pino, A.; Caruso, E.; Costanzo, L.; Guccione, P. A novel RyR2 mutation in a 2-year-old baby presenting with atrial fibrillation, atrial flutter, and atrial ectopic tachycardia. Heart Rhythm, 2014, 11, 1480-1483.
Zhabyeyev, P.; Hiess, F.; Wang, R.; Liu, Y.; Wayne Chen, S.R.; Oudit, G.Y. S4153R is a gain-of-function mutation in the cardiac Ca(2+) release channel ryanodine receptor associated with catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation. Can. J. Cardiol., 2013, 29, 993-996.
Kazemian, P.; Gollob, M.H.; Pantano, A.; Oudit, G.Y. A novel mutation in the RYR2 gene leading to catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation: dose-dependent arrhythmia-event suppression by β-blocker therapy. Can. J. Cardiol., 2011, 27, 870.e7-870.e10.
Zhang, Y.; Fraser, J.A.; Jeevaratnam, K.; Hao, X.; Hothi, S.S.; Grace, A.A.; Lei, M.; Huang, C.L. Acute atrial arrhythmogenicity and altered Ca(2+) homeostasis in murine RyR2-P2328S hearts. Cardiovasc. Res., 2011, 89, 794-804.
Thibodeau, I.L.; Xu, J.; Li, Q.; Liu, G.; Lam, K.; Veinot, J.P.; Birnie, D.H.; Jones, D.L.; Krahn, A.D.; Lemery, R.; Nicholson, B.J.; Gollob, M.H. Paradigm of genetic mosaicism and lone atrial fibrillation: physiological characterization of a connexin 43-deletion mutant identified from atrial tissue. Circulation, 2010, 122, 236-244.
Tuomi, J.M.; Tyml, K.; Jones, D.L. Atrial tachycardia/fibrillation in the connexin 43 G60S mutant (Oculodentodigital dysplasia) mouse. Am. J. Physiol. Heart Circ. Physiol., 2011, 300, H1402-H1411.
Delmar, M.; Makita, N. Cardiac connexins, mutations and arrhythmias. Curr. Opin. Cardiol., 2012, 27, 236-241.
Gollob, M.H.; Jones, D.L.; Krahn, A.D.; Danis, L.; Gong, X.Q.; Shao, Q.; Liu, X.; Veinot, J.P.; Tang, A.S.; Stewart, A.F.; Tesson, F.; Klein, G.J.; Yee, R.; Skanes, A.C.; Guiraudon, G.M.; Ebihara, L.; Bai, D. Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation. N. Engl. J. Med., 2006, 354, 2677-2688.
Yang, Y.Q.; Liu, X.; Zhang, X.L.; Wang, X.H.; Tan, H.W.; Shi, H.F.; Jiang, W.F.; Fang, W.Y. Novel connexin40 missense mutations in patients with familial atrial fibrillation. Europace, 2010, 12, 1421-1427.
Yang, Y.Q.; Zhang, X.L.; Wang, X.H.; Tan, H.W.; Shi, H.F.; Jiang, W.F.; Fang, W.Y.; Liu, X. Connexin40 nonsense mutation in familial atrial fibrillation. Int. J. Mol. Med., 2010, 26, 605-610.
Gemel, J.; Simon, A.R.; Patel, D.; Xu, Q.; Matiukas, A.; Veenstra, R.D.; Beyer, E.C. Degradation of a connexin40 mutant linked to atrial fibrillation is accelerated. J. Mol. Cell. Cardiol., 2014, 74, 330-339.
Sun, Y.; Hills, M.D.; Ye, W.G.; Tong, X.; Bai, D. Atrial fibrillation-linked germline GJA5/connexin40 mutants showed an increased hemichannel function. PLoS One, 2014, 9e95125
Sun, Y.; Tong, X.; Chen, H.; Huang, T.; Shao, Q.; Huang, W.; Laird, D.W.; Bai, D. An atrial-fibrillation-linked connexin40 mutant is retained in the endoplasmic reticulum and impairs the function of atrial gap-junction channels. Dis. Model. Mech., 2014, 7, 561-569.
Patel, D.; Gemel, J.; Xu, Q.; Simon, A.R.; Lin, X.; Matiukas, A.; Beyer, E.C.; Veenstra, R.D. Atrial fibrillation-associated connexin40 mutants make hemichannels and synergistically form gap junction channels with novel properties. FEBS Lett., 2014, 588, 1458-1464.
Bai, D. Atrial fibrillation-linked GJA5/connexin40 mutants impaired gap junctions via different mechanisms. FEBS Lett., 2014, 588, 1238-1243.
Postma, A.V.; van de Meerakker, J.B.; Mathijssen, I.B.; Barnett, P.; Christoffels, V.M.; Ilgun, A.; Lam, J.; Wilde, A.A.; Lekanne Deprez, R.H.; Moorman, A.F. A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation. Circ. Res., 2008, 102, 1433-1442.
Gutierrez-Roelens, I.; De Roy, L.; Ovaert, C.; Sluysmans, T.; Devriendt, K.; Brunner, H.G.; Vikkula, M. A novel CSX/NKX2-5 mutation causes autosomal-dominant AV block: are atrial fibrillation and syncopes part of the phenotype? Eur. J. Hum. Genet., 2006, 14, 1313-1316.
Huang, R.T.; Xue, S.; Xu, Y.J.; Zhou, M.; Yang, Y.Q. A novel NKX2.5 loss-of-function mutation responsible for familial atrial fibrillation. Int. J. Mol. Med., 2013, 31, 1119-1126.
Xie, W.H.; Chang, C.; Xu, Y.J.; Li, R.G.; Qu, X.K.; Fang, W.Y.; Liu, X.; Yang, Y.Q. Prevalence and spectrum of Nkx2.5 mutations associated with idiopathic atrial fibrillation. Clinics , 2013, 68, 777-784.
Yu, H.; Xu, J.H.; Song, H.M.; Zhao, L.; Xu, W.J.; Wang, J.; Li, R.G.; Xu, L.; Jiang, W.F.; Qiu, X.B.; Jiang, J.Q.; Qu, X.K.; Liu, X.; Fang, W.Y.; Jiang, J.F.; Yang, Y.Q. Mutational spectrum of the NKX2-5 gene in patients with lone atrial fibrillation. Int. J. Med. Sci., 2014, 11, 554-563.
Yuan, F.; Qiu, X.B.; Li, R.G.; Qu, X.K.; Wang, J.; Xu, Y.J.; Liu, X.; Fang, W.Y.; Yang, Y.Q.; Liao, D.N. A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias. Int. J. Mol. Med., 2015, 35, 478-486.
Wang, J.; Zhang, D.F.; Sun, Y.M.; Li, R.G.; Qiu, X.B.; Qu, X.K.; Liu, X.; Fang, W.Y. Yang YQ3. NKX2-6 mutation predisposes to familial atrial fibrillation. Int. J. Mol. Med., 2014, 34, 1581-1590.
Wang, J.; Zhang, D.F.; Sun, Y.M.; Yang, Y.Q. A novel PITX2c loss-of-function mutation associated with familial atrial fibrillation. Eur. J. Med. Genet., 2014, 57, 25-31.
Zhou, Y.M.; Zheng, P.X.; Yang, Y.Q.; Ge, Z.M.; Kang, W.Q. A novel PITX2c lossoffunction mutation underlies lone atrial fibrillation. Int. J. Mol. Med., 2013, 32, 827-834.
Tsai, C.T.; Hsieh, C.S.; Chang, S.N.; Chuang, E.Y.; Juang, J.M.; Lin, L.Y.; Lai, L.P.; Hwang, J.J.; Chiang, F.T.; Lin, J. Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation. J. Med. Genet., 2015, 52, 28-36.
Li, Q.Y.; Newbury-Ecob, R.A.; Terrett, J.A.; Wilson, D.I.; Curtis, A.R.; Yi, C.H.; Gebuhr, T.; Bullen, P.J.; Robson, S.C.; Strachan, T.; Bonnet, D.; Lyonnet, S.; Young, I.D.; Raeburn, J.A.; Buckler, A.J.; Law, D.J.; Brook, J.D. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat. Genet., 1997, 15, 21-29.
Costa, M.W.; Guo, G.; Wolstein, O.; Vale, M.; Castro, M.L.; Wang, L.; Otway, R.; Riek, P.; Cochrane, N.; Furtado, M.; Semsarian, C.; Weintraub, R.G.; Yeoh, T.; Hayward, C.; Keogh, A.; Macdonald, P.; Feneley, M.; Graham, R.M.; Seidman, J.G.; Seidman, C.E.; Rosenthal, N.; Fatkin, D.; Harvey, R.P. Functional characterization of a novel mutation in NKX2-5 associated with congenital heart disease and adult-onset cardiomyopathy. Circ Cardiovasc Genet, 2013, 6, 238-247.
Qu, X.K.; Qiu, X.B.; Yuan, F.; Wang, J.; Zhao, C.M.; Liu, X.Y.; Zhang, X.L.; Li, R.G.; Xu, Y.J.; Hou, X.M.; Fang, W.Y.; Liu, X.; Yang, Y.Q. A novel NKX2.5 loss-of-function mutation associated with congenital bicuspid aortic valve. Am. J. Cardiol., 2014, 114, 1891-1895.
Wang, J.; Mao, J.H.; Ding, K.K.; Xu, W.J.; Liu, X.Y.; Qiu, X.B.; Li, R.G.; Qu, X.K.; Xu, Y.J.; Huang, R.T.; Xue, S.; Yang, Y.Q. A novel NKX2.6 mutation associated with congenital ventricular septal defect. Pediatr. Cardiol., 2015, 36, 646-656.
Lin, Y.; Guo, X.; Zhao, B.; Xu, W.J.; Liu, X.Y.; Qiu, X.B.; Li, R.G.; Qu, X.K.; Xu, Y.J.; Huang, R.T.; Xue, S.; Yang, Y.Q. Association analysis identifies new risk loci for congenital heart disease in Chinese populations. Nat. Commun., 2015, 6, 8082.
Chowdhury, R.; Ashraf, H.; Melanson, M.; Tanada, Y.; Nguyen, M.; Silberbach, M.; Wakimoto, H.; Benson, D.W.; Anderson, R.H.; Kasahara, H. A mouse model of human congenital heart disease: progressive atrioventricular block induced by a heterozygous nkx2-5 homeodomain missense mutation. Circ Arrhythm Electrophysiol, 2015, 8, 1255-1264.
Zhou, W.; Zhao, L.; Jiang, J.Q.; Jiang, W.F.; Yang, Y.Q.; Qiu, X.B. A novel TBX5 loss-of-function mutation associated with sporadic dilated cardiomyopathy. Int. J. Mol. Med., 2015, 36, 282-288.
Zhao, L.; Ni, S.H.; Liu, X.Y.; Wei, D.; Yuan, F.; Xu, L.; Li, X.; Li, R.G.; Qu, X.K.; Xu, Y.J.; Fang, W.Y.; Yang, Y.Q.; Qiu, X.B. Prevalence and spectrum of Nkx2.6 mutations in patients with congenital heart disease. Eur. J. Med. Genet., 2014, 57, 579-586.
Wang, J.; Zhang, D.F.; Sun, Y.M.; Li, R.G.; Qiu, X.B.; Qu, X.K.; Liu, X.; Fang, W.Y.; Yang, Y.Q. NKX2-6 mutation predisposes to familial atrial fibrillation. Int. J. Mol. Med., 2014, 34, 1581-1590.
Ta-Shma, A.; El-lahham, N.; Edvardson, S.; Stepensky, P.; Nir, A.; Perles, Z.; Gavri, S.; Golender, J.; Yaakobi-Simhayoff, N.; Shaag, A.; Rein, A.J.; Elpeleg, O. Conotruncal malformations and absent thymus due to a deleterious NKX2-6 mutation. J. Med. Genet., 2014, 51, 268-270.
Heathcote, K.; Braybrook, C.; Abushaban, L.; Guy, M.; Khetyar, M.E.; Patton, M.A.; Carter, N.D.; Scambler, P.J.; Syrris, P. Common arterial trunk associated with a homeodomain mutation of NKX2.6. Hum. Mol. Genet., 2005, 14, 585-593.
Smith, J.G.; Magnani, J.W.; Palmer, C.; Meng, Y.A.; Soliman, E.Z.; Musani, S.K.; Kerr, K.F.; Schnabel, R.B.; Lubitz, S.A.; Sotoodehnia, N.; Redline, S.; Pfeufer, A.; Müller, M.; Evans, D.S.; Nalls, M.A.; Liu, Y.; Newman, A.B.; Zonderman, A.B.; Evans, M.K.; Deo, R.; Ellinor, P.T.; Paltoo, D.N.; Newton-Cheh, C.; Benjamin, E.J.; Mehra, R.; Alonso, A.; Heckbert, S.R.; Fox, E.R. Candidate-gene Association Resource (CARe) Consortium. Genome-wide association studies of the PR interval in African Americans. PLoS Genet., 2011, 7e1001304
den Hoed, M.; Eijgelsheim, M.; Esko, T. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nat. Genet., 2013, 45, 621-631.
Mohanty, S.; Santangeli, P.; Bai, R.; Mohanty, P.; Pump, A.; Natale, A. Variant rs2200733 on chromosome 4q25 confers increased risk of atrial fibrillation: evidence from a meta-analysis. J. Cardiovasc. Electrophysiol., 2013, 24, 155-161.
Olesen, M.S.; Holst, A.G.; Jabbari, J.; Nielsen, J.B.; Christophersen, I.E.; Sajadieh, A.; Haunsø, S.; Svendsen, J.H. Genetic loci on chromosomes 4q25, 7p31, and 12p12 are associated with onset of lone atrial fibrillation before the age of 40 years. Can. J. Cardiol., 2012, 28, 191-195.
Henningsen, K.M.; Olesen, M.S.; Haunsoe, S.; Svendsen, J.H. Association of rs2200733 at 4q25 with early onset of lone atrial fibrillation in young patients. Scand. Cardiovasc. J., 2011, 45, 324-326.
Kiliszek, M.; Franaszczyk, M.; Kozluk, E.; Lodzinski, P.; Piatkowska, A.; Broda, G.; Ploski, R.; Opolski, G. Association between variants on chromosome 4q25, 16q22 and 1q21 and atrial fibrillation in the Polish population. PLoS One, 2011, 6(7)e21790
Chinchilla, A.; Daimi, H.; Lozano-Velasco, E.; Dominguez, J.N.; Caballero, R.; Delpón, E.; Tamargo, J.; Cinca, J.; Hove-Madsen, L.; Aranega, A.E.; Franco, D. PITX2 insufficiency leads to atrial electrical and structural remodeling linked to arrhythmogenesis. Circ Cardiovasc Genet, 2011, 4, 269-279.
Wang, J.; Klysik, E.; Sood, S.; Johnson, R.L.; Wehrens, X.H.; Martin, J.F. Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification. Proc. Natl. Acad. Sci. USA, 2010, 107, 9753-9758.
Kirchhof, P.; Kahr, P.C.; Kaese, S.; Piccini, I.; Vokshi, I.; Scheld, H.H.; Rotering, H.; Fortmueller, L.; Laakmann, S.; Verheule, S.; Schotten, U.; Fabritz, L.; Brown, N.A. PITX2c is expressed in the adult left atrium, and reducing Pitx2c expression promotes atrial fibrillation inducibility and complex changes in gene expression. Circ Cardiovasc Genet, 2011, 4, 123-133.
Semina, E.V.; Reiter, R.; Leysens, N.J. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat. Genet., 1996, 14, 392-399.
Gage, P.J.; Camper, S.A. Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation. Hum. Mol. Genet., 1997, 6, 457-464.
St Amand, T.R.; Ra, J.; Zhang, Y. Cloning and expression pattern of chicken PITX2: A new component in the SHH signaling pathway controlling embryonic heart looping. Biochem. Biophys. Res. Commun., 1998, 247, 100-105.
Campione, M.; Steinbeisser, H.; Schweickert, A. The homeobox gene PITX2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping. Development, 1999, 126, 1225-1234.
Tümer, Z.; Bach-Holm, D. Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur. J. Hum. Genet., 2009, 17, 1527-1539.
Cox, C.J.; Espinoza, H.M.; McWilliams, B. Differential regulation of gene expression by PITX2 isoforms. J. Biol. Chem., 2002, 77, 25001-25010.
Logan, M.; Pagan-Westphal, S.M.; Smith, D.M.; Paganessi, L.; Tabin, C.J. The transcription factor PITX2 mediates situs-specific morphogenesis in response to left-right asymmetric signals. Cell, 1998, 94, 307-317.
Piedra, M.E.; Icardo, J.M.; Albajar, M.; Rodriguez-Rey, J.C.; Ros, M.A. PITX2 participates in the late phase of the pathway controlling left-right asymmetry. Cell, 1998, 94, 319-324.
Long, S.; Ahmad, N.; Rebagliati, M. The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry. Development, 2003, 130, 2303-2316.
Bisgrove, B.W.; Essner, J.J.; Yost, H.J. Multiple pathways in the midline regulate concordant brain, heart and gut left-right asymmetry. Development, 2000, 127, 3567-3579.
Guioli, S.; Lovell-Badge, R. PITX2 controls asymmetric gonadal development in both sexes of the chick and can rescue the degeneration of the right ovary. Development, 2007, 134, 4199-4208.
Lin, C.R.; Kioussi, C.; O’Connell, S.; Briata, P.; Szeto, D.; Liu, F.; Izpisúa-Belmonte, J.C.; Rosenfeld, M.G. PITX2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis. Nature, 1999, 401, 279-282.
Lu, M.F.; Pressman, C.; Dyer, R.; Johnson, R.L.; Martin, J.F. Function of Rieger syndrome gene in left-right asymmetry and craniofacial development. Nature, 1999, 401, 276-278.
Mommersteeg, M.T.; Brown, N.A.; Prall, O.W.J.; de Gier-de Vries, C.; Harvey, R.P.; Moorman, A.F.; Christoffels, V.M. PITX2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium. Circ. Res., 2007, 101, 902-909.
Aguirre, L.A.; Alonso, M.E.; Badía-Careaga, C.; Rollán, I.; Arias, C.; Fernández-Miñán, A.; López-Jiménez, E.; Aránega, A.; Gómez-Skarmeta, J.L.; Franco, D. Long-range regulatory interactions at the 4q25 atrial fibrillation risk locus involve PITX2c and ENPEP. BMC Biol., 2015, 13, 26.
Ye, J.; Tucker, N.R.; Weng, L.C.; Clauss, S.; Lubitz, S.A.; Ellinor, P.T. A functional variant associated with atrial fibrillation Regulates PITX2c expression through TFAP2a. Am. J. Hum. Genet., 2016, 99, 1281-1291.
Tao, Y.; Zhang, M.; Li, L.; Bai, Y.; Zhou, Y.; Moon, A.M.; Kaminski, H.J.; Martin, J.F. Pitx2, an atrial fibrillation predisposition gene, directly regulates ion transport and intercalated disc genes. Circ Cardiovasc Genet, 2014, 7, 23-32.
Lozano-Velasco, E.; Hernández-Torres, F.; Daimi, H.; Serra, S.A.; Herraiz, A.; Hove-Madsen, L.; Aránega, A.; Franco, D. Pitx2 impairs calcium handling in a dose-dependent manner by modulating Wnt signalling. Cardiovasc. Res., 2016, 109, 55-66.
Pérez-Hernández, M.; Matamoros, M.; Barana, A.; Amorós, I.; Gómez, R.; Núñez, M.; Sacristán, S.; Pinto, Á.; Fernández-Avilés, F.; Tamargo, J.; Delpón, E.; Caballero, R. Pitx2c increases in atrial myocytes from chronic atrial fibrillation patients enhancing IKs and decreasing ICa,L. Cardiovasc. Res., 2016, 109, 431-441.
Syeda, F.; Holmes, A.P.; Yu, T.Y.; Tull, S.; Kuhlmann, S.M.; Pavlovic, D.; Betney, D.; Riley, G.; Kucera, J.P.; Jousset, F.; de Groot, J.R.; Rohr, S.; Brown, N.A.; Fabritz, L.; Kirchhof, P. Pitx2 modulates atrial membrane potential and the antiarrhythmic effects of sodium-channel blockers. J. Am. Coll. Cardiol., 2016, 68, 1881-1894.
Nadadur, R.D.; Broman, M.T.; Boukens, B.; Mazurek, S.R.; Yang, X.; van den Boogaard, M.; Bekeny, J.; Gadek, M.; Ward, T.; Zhang, M.; Qiao, Y.; Martin, J.F.; Seidman, C.E.; Seidman, J.; Christoffels, V.; Efimov, I.R.; McNally, E.M.; Weber, C.R.; Moskowitz, I.P. Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm. Sci. Transl. Med., 2016, 8(354)354ra115
Franco & Aranega AE PITX2 (Pituitary Homeobox Gene 2). Encyclopedia of Signalling Molecules, Springer Nature. , 4024-4032.
Franco, D.; Chinchilla, A.; Aránega, A.E. Transgenic insights linking Pitx2 and atrial arrhythmias. Front. Physiol., 2012, 3, 206.
Lee, J.Y.; Kim, T.H.; Yang, P.S.; Lim, H.E.; Choi, E.K.; Shim, J.; Shin, E.; Uhm, J.S.; Kim, J.S.; Joung, B.; Oh, S.; Lee, M.H.; Kim, Y.H.; Pak, H.N. Korean atrial fibrillation network genome-wide association study for early-onset atrial fibrillation identifies novel susceptibility loci. Eur. Heart J., 2017, 38, 2586-2594.
Thorolfsdottir, R.B.; Sveinbjornsson, G.; Sulem, P.; Helgadottir, A.; Gretarsdottir, S.; Benonisdottir, S.; Magnusdottir, A.; Davidsson, O.B.; Rajamani, S.; Roden, D.M.; Darbar, D.; Pedersen, T.R.; Sabatine, M.S.; Jonsdottir, I.; Arnar, D.O.; Thorsteinsdottir, U.; Gudbjartsson, D.F.; Holm, H.; Stefansson, K. A missense variant in plec increases risk of atrial fibrillation. J. Am. Coll. Cardiol., 2017, 70, 2157-2168.
Nielsen, J.B.; Fritsche, L.G.; Zhou, W.; Teslovich, T.M.; Holmen, O.L.; Gustafsson, S.; Gabrielsen, M.E.; Schmidt, E.M.; Beaumont, R.; Wolford, B.N.; Lin, M.; Brummett, C.M.; Preuss, M.H.; Refsgaard, L.; Bottinger, E.P.; Graham, S.E.; Surakka, I. 1.; Chu, Y.; Skogholt, A.H.; Dalen, H.; Boyle, A.P.; Oral, H.; Herron, T.J.; Kitzman, J.; Jalife, J.; Svendsen, J.H.; Olesen, M.S.; Njølstad, I.; Løchen, M.L.; Baras, A.; Gottesman, O.; Marcketta, A.; O’Dushlaine, C.; Ritchie, M.D.; Wilsgaard, T.; Loos, R.J.F.; Frayling, T.M.; Boehnke, M.; Ingelsson, E.; Carey, D.J; Dewey, F.E.; Kang, H.M.; Abecasis, G.R.; Hveem, K.; Willer, C.J. Genome-wide study of atrial fibrillation identifies seven risk loci and highlights biological pathways and regulatory elements involved in cardiac development. Am. J. Hum. Genet., 2018, 102, 103-115.
Milan, D. The com-PLEC-sity of atrial fibrillation genetics. J. Am. Coll. Cardiol., 2017, 70, 2169-2170.
Bapat, A.; Anderson, C.D.; Ellinor, P.T.; Lubitz, S.A. Genomic basis of atrial fibrillation. Heart, 2018, 104, 201-206.
Tsai, C.T.; Hsieh, C.S.; Chang, S.N.; Chuang, E.Y.; Juang, J.M.; Lin, L.Y.; Lai, L.P.; Hwang, J.J.; Chiang, F.T.; Lin, J.L. Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation. J. Med. Genet., 2015, 52, 28-36.
Huang, Y.; Wang, C.; Yao, Y.; Zuo, X.; Chen, S.; Xu, C.; Zhang, H.; Lu, Q.; Chang, L.; Wang, F.; Wang, P.; Zhang, R.; Hu, Z.; Song, Q.; Yang, X.; Li, C.; Li, S.; Zhao, Y.; Yang, Q.; Yin, D.; Wang, X.; Si, W.; Li, X.; Xiong, X.; Wang, D.; Huang, Y.; Luo, C.; Li, J.; Wang, J.; Chen, J.; Wang, L.; Wang, L.; Han, M.; Ye, J.; Chen, F.; Liu, J.; Liu, Y.; Wu, G.; Yang, B.; Cheng, X.; Liao, Y.; Wu, Y.; Ke, T.; Chen, Q.; Tu, X.; Elston, R.; Rao, S.; Yang, Y.; Xia, Y.; Wang, Q.K. Molecular basis of gene-gene interaction: Cyclic cross-regulation of gene expression and post-gwas gene-gene interaction involved in atrial fibrillation. PLoS Genet., 2015, 11 e1005393
Kääb, S.; Darbar, D.; van Noord, C.; Dupuis, J.; Pfeufer, A.; Newton-Cheh, C.; Schnabel, R.; Makino, S.; Sinner, M.F.; Kannankeril, P.J.; Beckmann, B.M.; Choudry, S.; Donahue, B.S.; Heeringa, J.; Perz, S.; Lunetta, K.L.; Larson, M.G.; Levy, D.; MacRae, C.A.; Ruskin, J.N.; Wacker, A.; Schömig, A.; Wichmann, H.E.; Steinbeck, G.; Meitinger, T.; Uitterlinden, A.G.; Witteman, J.C.; Roden, D.M.; Benjamin, E.J.; Ellinor, P.T. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur. Heart J., 2009, 30, 813-819.
Li, G.; Zhang, R.; Gao, L.; Zhang, S.; Dong, Y.; Yin, X.; Chang, D.; Yang, Y.; Xia, Y. Lack of association between rs3807989 in cav1 and atrial fibrillation. Int. J. Clin. Exp. Pathol., 2014, 7, 4339-4344.
Tada, H.; Shiffman, D.; Smith, J.G.; Sjögren, M.; Lubitz, S.A.; Ellinor, P.T.; Louie, J.Z.; Catanese, J.J.; Engström, G.; Devlin, J.J.; Kathiresan, S.; Melander, O. Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke. Stroke, 2014, 45, 2856-2862.
Mahida, S.; Mills, R.W.; Tucker, N.R.; Simonson, B.; Macri, V.; Lemoine, M.D.; Das, S.; Milan, D.J.; Ellinor, P.T. Overexpression of KCNN3 results in sudden cardiac death. Cardiovasc. Res., 2014, 101, 326-334.
Jiang, Q.; Ni, B.; Shi, J.; Han, Z.; Qi, R.; Xu, W.; Wang, D.; Wang, D.W.; Chen, M. Down-regulation of ATBF1 activates STAT3 signaling via PIAS3 in pacing-induced HL-1 atrial myocytes. Biochem. Biophys. Res. Commun., 2014, 449, 278-283.
Tucker, N.R.; Dolmatova, E.V.; Lin, H.; Cooper, R.R.; Ye, J.; Hucker, W.J.; Jameson, H.S.; Parsons, V.A.; Weng, L.C.; Mills, R.W.; Sinner, M.F.; Imakaev, M.1.; Leyton-Mange, J.; Vlahakes, G.; Benjamin, E.J.; Lunetta, K.L.; Lubitz, S.A.; Mirny, L.; Milan, D.J.; Ellinor, P.T. Diminished PRRX1 expression is associated with increased risk of atrial fibrillation and shortening of the cardiac action potential. Circ Cardiovasc Genet, 2017, 10 pii: e001902
Seid, M.D.; Stein, J.; Hamer, S.; Pluteanu, F.; Scholz, B.; Wardelmann, E.; Huge, A.; Witten, A.; Stoll, M.; Hammer, E.; Völker, U.; Müller, F.U. Characterization of the genetic program linked to the development of atrial fibrillation in CREM-IbΔC-X mice. Circ Arrhythm Electrophysiol, 2017, 10 pii: e005075
Franco, D.; Lozano-Velasco, E.; Aranega, A. Gene regulatory networks in atrial fibrillation. World J. Med. Genet., 2016, 6, 1-16.
Nagy, I.I.; Railo, A.; Rapila, R.; Hast, T.; Sormunen, R.; Tavi, P.; Räsänen, J.; Vainio, S.J. Wnt-11 signalling controls ventricular myocardium development by patterning N-cadherin and beta-catenin expression. Cardiovasc. Res., 2010, 85, 100-109.
Pandur, P.; Läsche, M.; Eisenberg, L.M.; Kühl, M. Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature, 2002, 418, 636-641.
Martin, A.; Maher, S.; Summerhurst, K.; Davidson, D.; Murphy, P. Differential deployment of paralogous Wnt genes in the mouse and chick embryo during development. Evol. Dev., 2012, 14, 178-195.
Espinoza-Lewis, R.A.; Wang, D.Z. MicroRNAs in heart development. Curr. Top. Dev. Biol., 2012, 100, 279-317.
Franco, D.; Aranega, A. Post-transcriptional regulatory mechanisms. In: Clinic, Genetics and Molecular Pathways of Congenital Heart Diseases Eds Sperling S, Driscoll D, Kelly R. Springer. 2015.
Zhou, J.; Dong, X.; Zhou, Q.; Wang, H.; Qian, Y.; Tian, W.; Ma, D.; Li, X. microRNA expression profiling of heart tissue during fetal development. Int. J. Mol. Med., 2014, 33, 1250-1260.
Hu, D.L.; Liu, Y.Q.; Chen, F.K.; Sheng, Y.H.; Yang, R.; Kong, X.Q.; Cao, K.J.; Zhang, J.S.; Qian, L.M. Differential expression of microRNAs in cardiac myocytes compared to undifferentiated P19 cells. Int. J. Mol. Med., 2011, 28, 59-64.
Synnergren, J.; Améen, C.; Lindahl, A.; Olsson, B.; Sartipy, P. Expression of microRNAs and their target mRNAs in human stem cell-derived cardiomyocyte clusters and in heart tissue. Physiol. Genomics, 2011, 43, 581-594.
Nishi, H.; Sakaguchi, T.; Miyagawa, S.; Yoshikawa, Y.; Fukushima, S.; Saito, S.; Ueno, T.; Kuratani, T.; Sawa, Y. Impact of microRNA expression in human atrial tissue in patients with atrial fibrillation undergoing cardiac surgery. PLoS One, 2013, 8e73397
Wang, J.; Wang, Y.; Han, J.; Li, Y.; Xie, C.; Xie, L.; Shi, J.; Zhang, J.; Yang, B.; Chen, D.; Meng, X. Integrated analysis of microRNA and mRNA expression profiles in the left atrium of patients with nonvalvular paroxysmal atrial fibrillation: Role of miR-146b-5p in atrial fibrosis. Heart Rhythm, 2015, 12, 1018-1026.
Li, M.; Zhang, J. Circulating MicroRNAs: Potential and emerging biomarkers for diagnosis of cardiovascular and cerebrovascular diseases. BioMed Res. Int., 2015, 2015730535
Orenes-Piñero, E.; Montoro-García, S.; Patel, J.V.; Valdés, M.; Marín, F.; Lip, G.Y. Role of microRNAs in cardiac remodelling: new insights and future perspectives. Int. J. Cardiol., 2013, 167, 1651-1659.
Poudel, P.; Xu, Y.; Cui, Z.; Sharma, D.; Tian, B.; Paudel, S. Atrial fibrillation: recent advances in understanding the role of microRNAs in atrial remodeling with an electrophysiological overview. Cardiology, 2015, 131, 58-67.
Gomes da Silva, A.M.; Silbiger, V.N. miRNAs as biomarkers of atrial fibrillation. Biomarkers, 2014, 19, 631-636.
Liu, Z.; Zhou, C.; Liu, Y.; Wang, S.; Ye, P.; Miao, X.; Xia, J. The expression levels of plasma microRNAs in atrial fibrillation patients. PLoS One, 2012, 7e44906
Huang, Y.; Wang, C.; Yao, Y.; Zuo, X.; Chen, S.; Xu, C.; Zhang, H.; Lu, Q.; Chang, L.; Wang, F.; Wang, P.; Zhang, R.; Hu, Z.; Song, Q.; Yang, X.; Li, C.; Li, S.; Zhao, Y.; Yang, Q.; Yin, D.; Wang, X.; Si, W.; Li, X.; Xiong, X.; Wang, D.; Huang, Y.; Luo, C.; Li, J.; Wang, J.; Chen, J.; Wang, L.; Wang, L.; Han, M.; Ye, J.; Chen, F.; Liu, J.; Liu, Y.; Wu, G.; Yang, B.; Cheng, X.; Liao, Y.; Wu, Y.; Ke, T.; Chen, Q.; Tu, X.; Elston, R.; Rao, S.; Yang, Y.; Xia, Y.; Wang, Q.K. Molecular basis of gene-gene interaction: Cyclic cross-regulation of gene expression and post-gwas gene-gene interaction involved in atrial fibrillation. PLoS Genet., 2015, 11e1005393
Wang, J.; Bai, Y.; Li, N.; Ye, W.; Zhang, M.; Greene, S.B.; Tao, Y.; Chen, Y.; Wehrens, X.H.; Martin, J.F. Pitx2-microRNA pathway that delimits sinoatrial node development and inhibits predisposition to atrial fibrillation. Proc. Natl. Acad. Sci. USA, 2014, 111, 9181-9186.
Chiang, D.Y.; Kongchan, N.; Beavers, D.L.; Alsina, K.M.; Voigt, N.; Neilson, J.R.; Jakob, H.; Martin, J.F.; Dobrev, D.; Wehrens, X.H.; Li, N. Loss of microRNA-106b-25 cluster promotes atrial fibrillation by enhancing ryanodine receptor type-2 expression and calcium release. Circ Arrhythm Electrophysiol, 2014, 7, 1214-1222.
Barana, A.; Matamoros, M.; Dolz-Gaitón, P.; Pérez-Hernández, M.; Amorós, I.; Núñez, M.; Sacristán, S.; Pedraz, Á.; Pinto, Á.; Fernández-Avilés, F.; Tamargo, J.; Delpón, E.; Caballero, R. Chronic atrial fibrillation increases microRNA-21 in human atrial myocytes decreasing L-type calcium current. Circ Arrhythm Electrophysiol, 2014, 7, 861-868.
Daimi, H.; Lozano-Velasco, E.; Haj Khelil, A.; Chibani, J.B.; Barana, A.; Amorós, I.; González de la Fuente, M.; Caballero, R.; Aranega, A.; Franco, D. Regulation of SCN5A by microRNAs: miR-219 modulates SCN5A transcript expression and the effects of flecainide intoxication in mice. Heart Rhythm, 2015, 12, 1333-1342.
Luo, X.; Pan, Z.; Shan, H.; Xiao, J.; Sun, X.; Wang, N.; Lin, H.; Xiao, L.; Maguy, A.; Qi, X.Y.; Li, Y.; Gao, X.; Dong, D.; Zhang, Y.; Bai, Y.; Ai, J.; Sun, L.; Lu, H.; Luo, X.Y.; Wang, Z.; Lu, Y.; Yang, B.; Nattel, S. MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation. J. Clin. Invest., 2013, 123, 1939-1951.
Jia, X.; Zheng, S.; Xie, X.; Zhang, Y.; Wang, W.; Wang, Z.; Zhang, Y.; Wang, J.; Gao, M.; Hou, Y. MicroRNA-1 accelerates the shortening of atrial effective refractory period by regulating KCNE1 and KCNB2 expression: an atrial tachypacing rabbit model. PLoS One, 2013, 8e85639
Li, Y.D.; Hong, Y.F.; Yusufuaji, Y.; Tang, B.P.; Zhou, X.H.; Xu, G.J.; Li, J.X.; Sun, L.; Zhang, J.H.; Xin, Q.; Xiong, J.; Ji, Y.T.; Zhang, Y. Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation. Mol. Med. Rep., 2015, 12, 3243-3248.
Schmitz, S.U.; Grote, P.; Herrmann, B.G. Mechanisms of long noncoding RNA function in development and disease. Cell. Mol. Life Sci., 2016, 73(13), 2491-2509.
Rosa, A.; Ballarino, M. Long noncoding RNA regulation of pluripotency; Stem Cells Intern, 2015.
Wapinski, O.; Chang, H.Y. Long noncoding RNAs and human disease. Trends Cell Biol., 2011, 21(6), 354-361.
Rackham, O.; Shearwood, A.M.J.; Mercer, T.R.; Davies, S.M.; Mattick, J.S.; Filipovska, A. Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins. RNA, 2011, 17(12), 2085-2093.
St Ecedil Pien, E.; Costa, M.C.; Kurc, S.; Drożdż, A.; Cortez-Dias, N.; Enguita, F.J. The circulating non-coding RNA landscape for biomarker research: lessons and prospects from cardiovascular diseases. Acta Pharmacol. Sin., 2018, 39(7), 1085-1099.
Su, Y.; Li, L.; Zhao, S.; Yue, Y.; Yang, S. The long noncoding RNA expression profiles of paroxysmal atrial fibrillation identified by microarray analysis. Gene, 2018, 642, 125-134.
Yu, X.J.; Zou, L.H.; Jin, J.H.; Xiao, F.; Li, L.; Liu, N.; Yang, J.F.; Zou, T. Long noncoding RNAs and novel inflammatory genes determined by RNA sequencing in human lymphocytes are up-regulated in permanent atrial fibrillation. Am. J. Transl. Res., 2017, 9(5), 2314-2326.
Ruan, Z.; Sun, X.; Sheng, H.; Zhu, L. Long non-coding RNA expression profile in atrial fibrillation. Int. J. Clin. Exp. Pathol., 2015, 8(7), 8402-8410.
Xu, Y.; Huang, R.; Gu, J.; Jiang, W. Identification of long non-coding RNAs as novel biomarker and potential therapeutic target for atrial fibrillation in old adults. Oncotarget, 2016, 7(10), 10803-10811.
Wang, W.; Wang, X.; Zhang, Y.; Li, Z.; Xie, X.; Wang, J.; Gao, M.; Zhang, S.; Hou, Y. Transcriptome analysis of canine cardiac fat pads: involvement of two novel long non-coding RNAs in atrial fibrillation neural remodeling. J. Cell. Biochem., 2015, 116(5), 809-821.
Gore-Panter, S.R.; Hsu, J.; Barnard, J.; Moravec, C.S.; Van Wagoner, D.R.; Chung, M.K.; Smith, J.D. PANCR, the PITX2 adjacent noncoding rna, is expressed in human left atria and regulates PITX2c expression. Circ Arrhythm Electrophysiol, 2016, 9(1)e003197
Holmes, A.P.; Kirchhof, P. Pitx2 Adjacent Noncoding RNA: A New, Long, Noncoding Kid on the 4q25 Block. Circ Arrhythm Electrophysiol, 2016, 9e003808
Li, Z.; Wang, X.; Wang, W.; Du, J.; Wei, J.; Zhang, Y.; Wang, J.; Hou, Y. Altered long non-coding RNA expression profile in rabbit atria with atrial fibrillation: TCONS_00075467 modulates atrial electrical remodeling by sponging miR-328 to regulate CACNA1C. J. Mol. Cell. Cardiol., 2017, 108, 73-85.
Scridon, A.; Fouilloux-Meugnier, E.; Loizon, E.; Rome, S.; Julien, C.; Barrès, C.; Chevalier, P. Long-standing arterial hypertension is associated with Pitx2 down-regulation in a rat model of spontaneous atrial tachyarrhythmias. Europace, 2015, 17, 160-165.
Lozano-Velasco, E.; Wangensteen, R.; Quesada, A.; Garcia-Padilla, C.; Osorio, J.A.; Ruiz-Torres, M.D.; Aranega, A.; Franco, D. Hyperthyroidism, but not hypertension, impairs PITX2 expression leading to Wnt-microRNA-ion channel remodeling. PLoS One, 2017, 12e0188473
Torrado, M.; Franco, D.; Hernández-Torres, F.; Crespo-Leiro, M.G.; Iglesias-Gil, C.; Castro-Beiras, A.; Mikhailov, A.T. Pitx2c is reactivated in the failing myocardium and stimulates myf5 expression in cultured cardiomyocytes. PLoS One, 2014, 9e90561
Jabbari, R.; Jabbari, J.; Glinge, C.; Risgaard, B.; Sattler, S.; Winkel, B.G.; Terkelsen, C.J.; Tilsted, H.H.; Jensen, L.O.; Hougaard, M.; Haunsø, S.; Engstrøm, T.; Albert, C.M.; Tfelt-Hansen, J. Association of common genetic variants related to atrial fibrillation and the risk of ventricular fibrillation in the setting of first ST-elevation myocardial infarction. BMC Med. Genet., 2017, 18, 138.
Chinchilla, A.; Esteban, F.J.; Lozano-Velasco, E. Ventricular chamber-specific Pitx2 insufficiency leads to cardiac hypertrophy and arrhythmias. bioRxiv, , 253062. 2018
Weng, L.C.; Lunetta, K.L.; Müller-Nurasyid, M. Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium. Sci. Rep., 2017, 7, 11303.
Shoemaker, M.B.; Bollmann, A.; Lubitz, S.A.; Ueberham, L.; Saini, H.; Montgomery, J.; Edwards, T.; Yoneda, Z.; Sinner, M.F.; Arya, A.; Sommer, P.; Delaney, J.; Goyal, S.K.; Saavedra, P.; Kanagasundram, A.; Whalen, S.P.; Roden, D.M.; Hindricks, G.; Ellis, C.R.; Ellinor, P.T.; Darbar, D.; Husser, D. Common genetic variants and response to atrial fibrillation ablation. Circ Arrhythm Electrophysiol, 2015, 8, 296-302.
Kristjansson, R.P.; Benonisdottir, S.; Oddsson, A.; Galesloot, T.E.; Thorleifsson, G.; Aben, K.K.; Davidsson, O.B.; Jonsson, S.; Arnadottir, G.A.; Jensson, B.O.; Walters, G.B.; Sigurdsson, J.K.; Sigurdsson, S.; Holm, H.; Arnar, D.O.; Thorgeirsson, G.; Alexiusdottir, K.; Jonsdottir, I. Thorsteinsdottir, U.; Kiemeney, L.A.; Jonsson, T.; Gudbjartsson, D.F.; Rafnar, T.; Sulem, P.; Stefansson, K. Sequence variant at 4q25 near PITX2 associates with appendicitis. Sci. Rep., 2017, 7, 3119.
Mora, C.; Serzanti, M.; Giacomelli, A.; Beltramone, S.; Marchina, E.; Bertini, V.; Piovani, G.; Refsgaard, L.; Olesen, M.S.; Cortellini, V.; Dell’Era, P. Generation of induced pluripotent stem cells (iPSC) from an atrial fibrillation patient carrying a PITX2 p.M200V mutation. Stem Cell Res. , 2017, 24, 8-11.
Marczenke, M.; Fell, J.; Piccini, I.; Röpke, A.; Seebohm, G.; Greber, B. Generation and cardiac subtype-specific differentiation of PITX2-deficient human iPS cell lines for exploring familial atrial fibrillation. Stem Cell Res. , 2017, 21, 26-28.
Boutilier, J.K.; Taylor, R.L.; Mann, T.; McNamara, E.; Hoffman, G.J.; Kenny, J.; Dilley, R.J.; Henry, P.; Morahan, G.; Laing, N.G.; Nowak, K.J. Gene expression networks in the murine pulmonary myocardium provide insight into the pathobiology of atrial fibrillation. G3 (Bethesda), 2017, 7, 2999-3017.

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Year: 2019
Page: [183 - 194]
Pages: 12
DOI: 10.2174/1871529X19666190206150349
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