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(Circulation. 2006;113:e709.)
© 2006 American Heart Association, Inc.

Correspondence

Letter Regarding Article by Burke et al, "Role of SCN5A Y1102 Polymorphism in Sudden Cardiac Death in Blacks"

Dörte Etzrodt, PhD; Eric Schulze-Bahr, MD, PhD

Interdisciplinary Centre for Clinical Research (IZKF), Department of Cardiology and Angiology, University Hospital Münster, Münster, Germany

To the Editor:

We would like to comment the article by Burke et al,¹ who reported in a postmortem study a genetic association of the SCN5A Y1102 allele (or Y1103, for the long-splice variant) and patients with sudden cardiac death in the black population (107 noncardiac control samples, 117 with organic heart disease, 40 with cardiac hypertrophy, and 25 with cardiac arrhythmias). Because of the presence of clearly differing allele frequencies, it was concluded that the Y1102 allele might represent a marker for sudden cardiac death in patients with cardiac hypertrophy or arrhythmias, respectively. Previously, another article² reported that the SCN5A Y1102 allele might be a risk factor for abnormal repolarization and ventricular arrhythmia occurrence. However, in this study, a gene-dosage effect of the Y1102 allele on the QT interval was not seen in the reported pedigree. The study by Burke et al also touches on the role of the Y1102 allele as an arrhythmia risk factor. Even though the allele distribution was found in the Hardy-Weinberg equilibrium, the power of the case-control study appears to be underpowered. We estimated the needed samples size (using the Genetic Power Calculator³), assuming 6 heterozygotes in control subjects (n=107; Y1102 allele frequency: 2.8%), 8 in group 3 (n=40; Y1102 allele frequency: 10%), and 7 in group 4 (n=25; Y1102 allele frequency: 14%). For a power of 80% and =0.05, the needed sample size for group 3 would be >70 and for group 4 >52.

Therefore, conclusions about potential roles of (ion channel) polymorphisms should be drawn in the setting of powerfully designed studies and confirmatory data.⁴ It is likely that future genetic studies resolving current problems of association studies⁴ will shed additional light on the modification of arrhythmia susceptibility by natural gene variance.^4,5

	Acknowledgments

 
Disclosures

None.

	References

Top References Acknowledgments  References

 

1. Burke A, Creighton W, Mont E, Li L, Hogan S, Kutys R, Fowler D, Virmani R. Role of SCN5A Y1102 polymorphism in sudden cardiac death in blacks. Circulation. 2005; 112: 798–802.[Abstract/Free Full Text]
   
2. Splawski I, Timothy KW, Tateyama M, Clancy C, Malhotra A, Beggs A, Cappuccio F, Sagnella G, Kass R, Keating M. Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science. 2002; 297: 1333–1336.[Abstract/Free Full Text]
   
3. Statistical Genetic Group. Genetic power calculator. Available at: http://pngu.mgh.harvard.edu/purcell/gpc/cc2.html. Accessed March 21, 2006.
   
4. Freely associating [Editorial]. Nat Genet. 1999; 22: 1–2.[CrossRef][Medline] [Order article via Infotrieve]
   
5. Kääb S, Schulze-Bahr E. Susceptibility genes and modifiers for cardiac arrhythmias. Cardiovasc Res. 2005; 67: 397–413.[CrossRef][Medline] [Order article via Infotrieve]
   

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Allen Burke, MD; Wendy Creighton, MD; Erik Mont, MD; Ling Li, MD; Susan Hogan, MD; Robert Kutys, MS; David Fowler, MD; Renu Virmani, MD

Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC

Response

We appreciate Dorte and Shulze-Barr’s comments about our article.¹ The statistics in our study used standard methods which, although valid, were not specific for calculating significance of differing allele frequencies. Therefore, we agree that confirmation of our findings in a larger group of patients and with family studies is essential in further substantiating our findings, which were initially suggested by Splawski et al.² We believe that there are a variety of methods for determining the role of mutations in sudden unexplained death in the absence of morphological substrates. Despite the limitations of autopsy studies, including relatively small numbers of rare events, complete cardiac morphological evaluation offered by autopsies represents, in our opinion, invaluable data for testing hypotheses regarding the link between genetic variations and lethal arrhythmias.

	Acknowledgments

Top References Acknowledgments  References

 
Disclosures

None.

	References

Top References Acknowledgments  References

 

1. Burke A, Creighton W, Mont E, Li L, Hogan S, Kutys R, Fowler D, Virmani R. Role of SCN5A Y1102 polymorphism in sudden cardiac death in blacks. Circulation. 2005; 112: 798–802.[Abstract/Free Full Text]
   
2. Splawski I, Timothy KW, Tateyama M, Clancy C, Malhotra A, Beggs A, Cappuccio F, Sagnella G, Kass R, Keating M. Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science. 2002; 297: 1333–1336.[Abstract/Free Full Text]
   

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Circulation 2006 113: 1817. [Full Text]

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