Atrial fibrillation is a complex disease. Its etiologies are diverse and genetic factors may also contribute to this disease. With the advent of modern molecular biology technology, it is now possible to explore the genetic components in the pathogenesis of atrial fibrillation. Past molecular genetic studies on atrial fibrillation in the literature can be divided into linkage analysis studies and association studies. The subjects for linkage analysis studies are pedigrees of probands with Mendelian hereditary atrial fibrillation. The first locus identified for autosomal dominant atrial fibrillation locates at 10q22–q24. However, the exact gene is still unknown. Another linkage analysis study in Chinese revealed that LQT1 gene (IKs α-subunit) was the responsible gene. A missense mutation in the IKs α-subunit results in a gain of function, which is important in causing atrial fibrillation. The third known locus for familial atrial fibrillation locates at 6q14–16. The responsible gene remains still unknown. The other type of studies takes the case-control design (association studies) and the subjects have multigenic atrial fibrillation. In a study in a Japanese population, it was reported that the angiotensin-converting enzyme insertion/deletion polymorphism was not associated with atrial fibrillation. On the other hand, researchers in Taiwan reported that a nonsynonymous single nucleotide polymorphism of the LQT5 gene (IKs β-subunit) is associated with atrial fibrillation. In summary, there is growing evidence showing that genetic factors are important in the pathogenesis of atrial fibrillation. We expect that more genes responsible for or contributing to atrial fibrillation will be identified in the future and these will elucidate the molecular mechanisms of atrial fibrillation.

Keywords:
Atrial fibrillation, Genetics, Linkage analysis, Potassium channel
1.
Kannel WB, Abbott RD, Savage DD, et al: Epidemiologic features of atrial fibrillation. N Engl J Med 1982;306:1018–1022.
2.
Onundarson PT, Thorgeirsson G, Jonmundsson E, et al: Chronic atrial fibrillation: Epidemiologic features and 14 year follow-up: A case control study. Eur Heart J 1987;8:521–527.
3.
Alpert JS, Petersen P, Godtfredsen J: Atrial fibrillation: Natural history, complications and management. Annu Rev Med 1988;39:41–52.
4.
Brugada R, Tapscott T, Czernuszewicz GZ, et al: Identification of a genetic locus for familial atrial fibrillation. N Engl J Med 1997;336:905–911.
5.
Shah G, Brugada R, Gonzalez O, Czernuszewicz G, Gibbs RA, Bachinski L, Roberts R: The cloning, genomic organization and tissue expression profile of the human DLG5 gene. BMC Genomics 2002;3:6.
6.
Chen YH, Xu SJ, Bendahhou S, et al: KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 2003;299:251–254.
7.
Wang Q, Curran ME, Splawski I, et al: Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 1996;12:17–23.
8.
Barhanin J, Lesage F, Guillemare E, et al: KvLQT1 and Isk (minK) proteins associate to form the Isk cardiac potassium current. Nature 1996;384:78–80.
9.
Sanguinetti MC, Curran ME, Zou A, et al: Coassembly of KvLQT1 and mink (IsK) proteins to form cardiac Iks potassium channel. Nature 1996;384:80–83.
10.
Abbott GW, Sesti F, Splawski I, et al: MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 1999;97:175–187.
11.
Moe GK: Evidence for reentry as a mechanism of cardiac arrhythmias. Rev Physiol Biochem Pharmacol 1975;72:55–81.
12.
Ellinor PT, Shin JT, Moore RK, Yoerger DM, MacRae CA: Locus for atrial fibrillation maps to chromosome 6q14–16. Circulation 2003;107:2880–2883.
13.
Yamashita T, Hayami N, Ajiki K, et al: Is ACE gene polymorphism associated with lone atrial fibrillation? Jpn Heart J 1997;38:637–641.
14.
Cambien F: The angiotensin-converting enzyme (ACE) genetic polymorphism: Its relationship with plasma ACE level and myocardial infarction. Clin Genet 1994;46:94–101.
15.
Lai LP, Su MJ, Yeh HM, Lin JL, Chiang FT, Hwang JJ, Hsu KL, Tseng CD, Lien WP, Tseng YZ, Huang SKS: Association of the human MinK gene 38G allele with atrial fibrillation: Evidence of possible genetic control on the pathogenesis of atrial fibrillation. Am Heart J 2002;144:485–490.
16.
Lai LP, Su MJ, Lin JL, Lin FY, Tsai CH, Chen YS, Tseng YZ, Lien WP, Huang SKS: Changes in the mRNA levels of delayed rectifier potassium channels in human atrial fibrillation. Cardiology 1999;92:248–255.
17.
Lai LP, Deng CL, Moss AJ, et al: Polymorphism of the gene encoding a human minimal potassium ion channel (minK). Gene 1994;151:339–340.
18.
Lai LP, Su MJ, Lin JL, et al: A study on two kinds of human minK proteins: Electrophysiological and pharmacological properties and incidence in the Chinese population. Acta Cardiol Sin 2000;16:221–228.
19.
Chiang CE, Roden DM: The long QT syndromes: Genetic basis and clinical implications. J Am Coll Cardiol 2000;36:1–12.
20.
Schott JJ, et al: Mapping of a gene for long QT syndrome to chromosome 4q25–27. Am J Hum Genet 1995;57:1114–1122.
21.
Mohler PJ, Schott JJ, Gramolini AO, Dilly KW, Guatimosim S, duBell WH, Song LS, Haurogne K, Kyndt F, Ali ME, Rogers TB, Lederer WJ, Escande D, Le Marec H, Bennett V: Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature 2003;421:634–639.
22.
Gollob MH, Green MS, Tang AS, Gollob T, Karibe A, Ali Hassan AS, Ahmad F, Lozado R, Shah G, Fananapazir L, Bachinski LL, Roberts R, Hassan AS: Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med 2001;344:1823–1831.
23.
Gollob MH, Seger JJ, Gollob TN, Tapscott T, Gonzales O, Bachinski L, Roberts R: Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation 2001;104:3030–3033.
24.
Robinson K, Frenneaux MP, Stockins B, Karatasakis G, Poloniecki JD, McKenna WJ: Atrial fibrillation in hypertrophic cardiomyopathy: A longitudinal study. J Am Coll Cardiol 1990;15:1279–1285.
25.
Sachdev B, Elliott PM, McKenna WJ: Cardiovascular complications of neuromuscular disorders. Curr Treat Options Cardiovasc Med 2002;4:171–179.
26.
Nakajima H, Nakajima HO, Salcher O, Dittie AS, Dembowsky K, Jing S, Field LJ: Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-beta(1) transgene in the heart. Circ Res 2000;86:571–579.
27.
Verheule S, van Batenburg CA, Coenjaerts FE, Kirchhoff S, Willecke K, Jongsma HJ: Cardiac conduction abnormalities in mice lacking the gap junction protein connexin40. J Cardiovasc Electrophysiol 1999;10:1380–1389.
28.
Lamarche J, O’Hara G, Philippon F, Gilbert M, Daleau P: Molecular analysis of connexin 40 in the familial form of atrial fibrillation. Eur Heart J 2001;22:1511–1512.
© 2003 S. Karger AG, Basel
2003
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.