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Author Notes:

Correspondence: A. Maziar Zafari, M.D., Ph.D., Division of Cardiology, Emory University, 1639 Pierce Dr., WMB 322, Atlanta, GA, 30322; Tel: (404) 727-4724; Fax:(404) 712-8335; Email: azafari@emory.edu.

and Charles D. Searles, M.D., Atlanta VAMC, 1670 Clairmont Rd., mailstop 111, Decatur, GA, 30033; Tel: (404) 321-6111; Fax: (404) 329-2211; Email: csearle@emory.edu

Disclosures: None

Subject:

Research Funding:

The Genetic Risk Assessment of Defibrillator Events (GRADE) study is supported by a NHLBI grant through an R01 mechanism (B. London).

This work was also supported by NIH T32HL007745 (R.R. Blanco); investigator-initiated grant from Medtronic, Inc. (A.M. Zafari); NHLBI Program of Excellence in Nanotechnology (HHSN268201000043C to CDS) and a NHLBI R01 Award (HL 109559 to CDS)

Keywords:

  • Genetic Polymorphisms
  • Angiotensin
  • Angiotensin Type 1 Receptor
  • Sudden Cardiac Death
  • Heart Failure
  • microRNA

Angiotensin Receptor Type 1 Single Nucleotide Polymorphism A1166C is Associated with Malignant Arrhythmias and Altered Circulating miR-155 Levels in Patients with Chronic Heart Failure

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Journal Title:

Journal of Cardiac Failure

Volume:

Volume 18, Number 9

Publisher:

, Pages 717-723

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background Sudden cardiac death (SCD) due to ventricular tachyarrhythmias accounts for approximately 450,000 annual deaths in the U.S.; many of these cases involve patients with chronic heart failure (HF). Prediction of which HF patients are most susceptible to SCD is difficult, and it is uncertain whether gene polymorphisms associated with HF outcomes are also linked to arrhythmic risk. Methods We evaluated 485 patients with chronic HF to see whether the Angiotensin Receptor Type 1 (AT1) A1166C or Angiotensin Converting Enzyme Insertion/Deletion (ACE I/D) polymorphisms were associated with a higher rate of ventricular arrhythmias requiring implantable cardioverter defibrillator (ICD) therapies over a 5-year period. We assessed the correlation between polymorphisms and antitachycardia pacing (ATP) and/or ICD shocks. Results Patients with AT1-1166 CC genotype had an increased rate of all events: ATP plus ICD shocks (p=0.02). There was no association between ACE I/D genotype and ICD therapies. Furthermore, circulating levels of microRNA-155 (miR-155), a microRNA known to posttranscriptionally regulate AT1R expression, were significantly decreased in the CC compared to the AC and AA genotypes and were associated with ICD events. Conclusion Our study suggests that the AT1R-1166 CC genotype is associated with increased ICD therapies in patients with chronic HF, and the level of circulating miR-155 may be a potential marker for arrhythmic risk. While these findings are novel, they will need replication and validation in larger cohorts of chronic HF patients.

Copyright information:

© 2012, Elsevier

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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