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

• Authors: Raul R. Blanco, Emory University; Harland Austin, Emory University; Richard N. Vest, Emory University; Ravinder Valadri, Emory University; Wei Li, Emory University; Bernard P Lassegue, Emory University; Qing Song, Morehouse School of Medicine; Barry London, University of Pittsburgh; Samuel C. Dudley, University of Illinois; Heather Bloom, Emory University; Charles D Searles Jr., Emory University; A. Maziar Zafari, Emory University
• Journal Title: Journal of Cardiac Failure
• Volume: Volume 18, Number 9
• Publisher: Elsevier | 2012-09, Pages 717-723
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.cardfail.2012.06.531
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Genetic Polymorphisms; Angiotensin; Angiotensin Type 1 Receptor; Sudden Cardiac Death; Heart Failure; microRNA

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.