This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bunch, T. J. Articles by Ackerman, M. J. Search for Related Content PubMed PubMed Citation Articles by Bunch, T. J. Articles by Ackerman, M. J. Related Collections Electrophysiology Clinical genetics Arrythmias-basic studies Functional genomics Genomics Ion channels/membrane transport Arrhythmias, clinical electrophysiology, drugs Genetics of cardiovascular disease Related Article

(Circulation. 2006;113:330-332.)
© 2006 American Heart Association, Inc.

Editorial

Promoting Arrhythmia Susceptibility

T. Jared Bunch, MD; Michael J. Ackerman, MD, PhD

From the Department of Internal Medicine, Division of Cardiovascular Medicine (T.J.B., M.J.A.), Department of Pediatrics, Division of Pediatric Cardiology (M.J.A.), and Department of Molecular Pharmacology and Experimental Therapeutics (M.J.A.), Mayo Clinic College of Medicine, Rochester, Minn.

Correspondence to Michael J. Ackerman, MD, PhD, Sudden Death Genomics Laboratory, Guggenheim 501, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail ackerman.michael@mayo.edu

Key Words: Editorials • arrhythmia • death, sudden • genes • long-QT syndrome

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The SCN5A-encoded voltage-gated cardiac sodium channel -subunit (hNaV1.5) is one of the critical ion channels necessary to orchestrate both the cardiac action potential and excitation-contraction coupling of the ventricular myocyte.¹ Rare mutations in SCN5A have been implicated in a cadre of the cardiac channelopathies, including congenital long-QT syndrome (LQTS), Brugada syndrome (BrS), progressive cardiac conduction disease, idiopathic ventricular fibrillation, autosomal recessive sick sinus syndrome, sudden infant death syndrome, and even a cardiomyopathic electropathy characterized by dilated cardiomyopathy, conduction disease, and atrial fibrillation.^1–9 In addition, some common nonsynonymous single nucleotide polymorphisms (cSNPs or coding polymorphisms) may increase the risk of drug-induced torsade de pointes and sudden cardiac death, particularly among blacks, whereas other cSNPs may result in a "reduced depolarization capacity."^10–12

Article p 338

Now, because of this international all-star cast of channelologists, the proverbial street lamp is shining on a new location in the SCN5A gene and has illuminated an excitingly novel genetic mechanism that may promote arrhythmia susceptibility. In this issue of Circulation, Bezzina and colleagues¹³ reveal their discovery of a novel ethnic-specific promoter variant (HapB) that may genetically reduce the "antifibrillatory reserve" of a host. To appreciate the magnitude of these investigators’ sleuthing, one must consider where the street lamp has been shining for the past decade.

Since the sentinel discovery of SCN5A as a disease gene for LQTS in 1995,¹ SCN5A genetic testing has focused on the 27 translated exons that encode the 2015 or 2016 amino acids of the channel (depending on which alternatively . . . [Full Text of this Article]

Related Article:

Common Sodium Channel Promoter Haplotype in Asian Subjects Underlies Variability in Cardiac Conduction

Connie R. Bezzina, Wataru Shimizu, Ping Yang, Tamara T. Koopmann, Michael W.T. Tanck, Yoshihiro Miyamoto, Shiro Kamakura, Dan M. Roden, and Arthur A.M. Wilde
Circulation 2006 113: 338-344. [Abstract] [Full Text]

This article has been cited by other articles:

				R. Shephard and C. Semsarian Advances in the prevention of sudden cardiac death in the young Therapeutic Advances in Cardiovascular Disease, April 1, 2009; 3(2): 145 - 155. [Abstract] [PDF]