Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

Overview

Journal Stroke Res Treat

Publisher Wiley

Date 2011 Aug 9

PMID 21822468

Citations 3

Authors

Robin Lemmens

Sylvia Hermans

Dieter Nuyens

Vincent Thijs

Affiliations

Soon will be listed here.

Abstract

Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart failure and ischemic stroke. Since atrial fibrillation can result in ischemic stroke, one might assume that genetic determinants of this cardiac arrhythmia are also implicated in cerebrovascular disease. Ischemic stroke is a multifactorial, complex disease where multiple environmental and genetic factors interact. Whether genetic variants associated with a risk factor for ischemic stroke also increase the risk of a particular vascular endpoint still needs to be confirmed in many cases. Here we review the current knowledge on the genetic background of atrial fibrillation and the consequences for cerebrovascular disease.

Citing Articles

New Radiomic Markers of Pulmonary Vein Morphology Associated With Post-Ablation Recurrence of Atrial Fibrillation.

Labarbera M, Atta-Fosu T, Feeny A, Firouznia M, Mchale M, Cantlay C IEEE J Transl Eng Health Med. 2022; 10:1800209.

PMID: 34976444 PMC: 8716081. DOI: 10.1109/JTEHM.2021.3134160.

Weighted gene coexpression network analysis of human left atrial tissue identifies gene modules associated with atrial fibrillation.

Tan N, Chung M, Smith J, Hsu J, Serre D, Newton D Circ Cardiovasc Genet. 2013; 6(4):362-71.

PMID: 23863953 PMC: 3955718. DOI: 10.1161/CIRCGENETICS.113.000133.

Advances in oral anticoagulation treatment: the safety and efficacy of rivaroxaban in the prevention and treatment of thromboembolism.

Turpie A Ther Adv Hematol. 2013; 3(5):309-323.

PMID: 23365716 PMC: 3546633. DOI: 10.1177/2040620712453067.

References

Chen Y, Xu S, Bendahhou S, Wang X, Wang Y, Xu W . KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science. 2003; 299(5604):251-4. DOI: 10.1126/science.1077771. View

Xia M, Jin Q, Bendahhou S, He Y, Larroque M, Chen Y . A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochem Biophys Res Commun. 2005; 332(4):1012-9. DOI: 10.1016/j.bbrc.2005.05.054. View

Ikram M, Seshadri S, Bis J, Fornage M, DeStefano A, Aulchenko Y . Genomewide association studies of stroke. N Engl J Med. 2009; 360(17):1718-28. PMC: 2768348. DOI: 10.1056/NEJMoa0900094. View

Das S, Makino S, Melman Y, Shea M, Goyal S, Rosenzweig A . Mutation in the S3 segment of KCNQ1 results in familial lone atrial fibrillation. Heart Rhythm. 2009; 6(8):1146-53. PMC: 3038671. DOI: 10.1016/j.hrthm.2009.04.015. View

Kirchhof P, Auricchio A, Bax J, Crijns H, Camm J, Diener H . Outcome parameters for trials in atrial fibrillation: executive summary. Eur Heart J. 2007; 28(22):2803-17. DOI: 10.1093/eurheartj/ehm358. View

Yang Y, Xia M, Jin Q, Bendahhou S, Shi J, Chen Y . Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am J Hum Genet. 2004; 75(5):899-905. PMC: 1182120. DOI: 10.1086/425342. View

Li Q, Huang H, Liu G, Lam K, Rutberg J, Green M . 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(1):132-7. DOI: 10.1016/j.bbrc.2009.01.052. View

Christophersen I, Steen Ravn L, Budtz-Joergensen E, Skytthe A, Haunsoe S, Svendsen J . Familial aggregation of atrial fibrillation: a study in Danish twins. Circ Arrhythm Electrophysiol. 2009; 2(4):378-83. PMC: 2760022. DOI: 10.1161/CIRCEP.108.786665. View

Lundby A, Steen Ravn L, Svendsen J, Olesen S, Schmitt N . KCNQ1 mutation Q147R is associated with atrial fibrillation and prolonged QT interval. Heart Rhythm. 2007; 4(12):1532-41. DOI: 10.1016/j.hrthm.2007.07.022. View

10.

Friberg L, Hammar N, Rosenqvist M . Digoxin in atrial fibrillation: report from the Stockholm Cohort study of Atrial Fibrillation (SCAF). Heart. 2009; 96(4):275-80. DOI: 10.1136/hrt.2009.175786. View

11.

Liu T, Korantzopoulos P, Xu G, Shehata M, Li D, Wang X . Association between angiotensin-converting enzyme insertion/deletion gene polymorphism and atrial fibrillation: a meta-analysis. Europace. 2010; 13(3):346-54. DOI: 10.1093/europace/euq407. View

12.

Kaab S, Darbar D, van Noord C, Dupuis J, Pfeufer A, Newton-Cheh C . Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J. 2009; 30(7):813-9. PMC: 2663727. DOI: 10.1093/eurheartj/ehn578. View

13.

Yang T, Yang P, Roden D, Darbar D . Novel KCNA5 mutation implicates tyrosine kinase signaling in human atrial fibrillation. Heart Rhythm. 2010; 7(9):1246-52. PMC: 2932792. DOI: 10.1016/j.hrthm.2010.05.032. View

14.

Firouzi M, Ramanna H, Kok B, Jongsma H, Koeleman B, Doevendans P . Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation. Circ Res. 2004; 95(4):e29-33. DOI: 10.1161/01.RES.0000141134.64811.0a. View

15.

Gschwendtner A, Bevan S, Cole J, Plourde A, Matarin M, Ross-Adams H . Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Ann Neurol. 2009; 65(5):531-9. PMC: 2702695. DOI: 10.1002/ana.21590. View

16.

Hagendorff A, Schumacher B, Kirchhoff S, Luderitz B, Willecke K . Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation. Circulation. 1999; 99(11):1508-15. DOI: 10.1161/01.cir.99.11.1508. View

17.

Sinner M, Pfeufer A, Akyol M, Beckmann B, Hinterseer M, Wacker A . The non-synonymous coding IKr-channel variant KCNH2-K897T is associated with atrial fibrillation: results from a systematic candidate gene-based analysis of KCNH2 (HERG). Eur Heart J. 2008; 29(7):907-14. DOI: 10.1093/eurheartj/ehm619. View

18.

Bedi M, McNamara D, London B, Schwartzman D . Genetic susceptibility to atrial fibrillation in patients with congestive heart failure. Heart Rhythm. 2006; 3(7):808-12. DOI: 10.1016/j.hrthm.2006.03.002. View

19.

Yang Y, Li J, Lin X, Yang Y, Hong K, Wang L . Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation. J Hum Genet. 2009; 54(5):277-83. DOI: 10.1038/jhg.2009.26. View

20.

Ruan Y, Liu N, Priori S . Sodium channel mutations and arrhythmias. Nat Rev Cardiol. 2009; 6(5):337-48. DOI: 10.1038/nrcardio.2009.44. View