Skip Navigation



European Heart Journal Advance Access published online on July 9, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn328
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
29/20/2514    most recent
ehn328v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Arvanitis, D. A.
Right arrow Articles by Kranias, E. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arvanitis, D. A.
Right arrow Articles by Kranias, E. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org.

The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy

Demetrios A. Arvanitis1, Despina Sanoudou1,{dagger}, Fotis Kolokathis2,{dagger}, Elizabeth Vafiadaki1, Vasiliki Papalouka1, Aikaterini Kontrogianni-Konstantopoulos3, George N. Theodorakis5, Ioannis A. Paraskevaidis2, Stamatios Adamopoulos5, Gerald W. Dorn, II4, Dimitrios Th. Kremastinos2 and Evangelia G. Kranias1,6,*

1 Molecular Biology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece
2 Second Department of Cardiology, University of Athens, Attikon Hospital, Athens, Greece
3 Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland Baltimore, Baltimore, MD, USA
4 Center for Molecular Cardiovascular Research, College of Medicine, University of Cincinnati, Cincinnati, OH, USA
5 Second Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece
6 Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0575, USA

Received 20 December 2007; revised 13 June 2008; accepted 19 June 2008.

* Corresponding author. Tel: +1 513 558 2377, Fax: +1 513 558 2269, Email: litsa.kranias{at}uc.edu

Aims: To investigate whether genetic variants of the histidine-rich calcium (HRC)-binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and its progression.

Methods and results: We screened 123 idiopathic DCM patients and 96 healthy individuals by single-strand conformation polymorphism analysis and direct sequencing for genetic variants in HRC. Six polymorphisms were detected: Leu35Leu (A/G), Ser43Asn (G/A), Ser96Ala (T/G), Glu202_Glu203insGlu (–/GAG), Asp261del (GAT/–), and an in-frame insertion of 51 amino acids at His321. The analysis of their frequencies did not reveal any significant correlation with DCM development. However, the Ser96Ala polymorphism exhibited a statistically significant correlation with the occurrence of life-threatening ventricular arrhythmias. During a follow-up of 4.02 ± 2.4 years, the risk for ventricular arrhythmias was higher (HR, 9.620; 95% CI, 2.183–42.394; P = 0.003) in the Ala/Ala patients, compared with Ser/Ser homozygous patients. On multivariable Cox regression analysis, the Ser96Ala polymorphism was the only significant genetic arrythmogenesis predictor in DCM patients (HR, 4.191; 95% CI, 0.838–20.967; P = 0.018).

Conclusion: The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.

Key Words: Calcium • Sarcoplasmic reticulum • Prognosis • Defibrillation

{dagger} D.S. and F.K. contributed equally to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Physiol.Home page
T. J. Pritchard and E. G. Kranias
Junctin and the histidine-rich Ca2+ binding protein: potential roles in heart failure and arrhythmogenesis
J. Physiol., July 1, 2009; 587(13): 3125 - 3133.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Q. Yuan, P. Han, M. Dong, X. Ren, X. Zhou, S. Chen, W. K. Jones, G. Chu, H.-S. Wang, and E. G. Kranias
Partial downregulation of junctin enhances cardiac calcium cycling without eliciting ventricular arrhythmias in mice
Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1484 - H1490.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.