Journal article
Angiotensin Receptor Type 1 Single Nucleotide Polymorphism 1166A/C is Associated With Malignant Arrhythmias and Altered Circulating miR-155 Levels in Patients With Chronic Heart Failure
Journal of cardiac failure, Vol.18(9), pp.717-723
09/01/2012
DOI: 10.1016/j.cardfail.2012.06.531
PMCID: PMC3640363
PMID: 22939041
Abstract
Background: Sudden cardiac death (SCD) from ventricular tachyarrhythmias accounts for approximately 450,000 annual deaths in the United States; 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 (AT1R) 1166A/C 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 AT1R-1166CC genotype had an increased rate of all events: ATP plus ICD shocks (P = .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 with the AC and AA genotypes and were associated with ICD events. Conclusion: Our study suggests that the AT1R-1166CC 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. Although these findings are novel, they will need replication and validation in larger cohorts of chronic HF patients. (J Cardiac Fail 2012;18:717-723)
Details
- Title: Subtitle
- Angiotensin Receptor Type 1 Single Nucleotide Polymorphism 1166A/C is Associated With Malignant Arrhythmias and Altered Circulating miR-155 Levels in Patients With Chronic Heart Failure
- Creators
- Raul R. Blanco - Emory UniversityHarland Austin - Emory UniversityRichard N. Vest - Emory UniversityRavinder Valadri - Emory UniversityWei Li - Emory UniversityBernard Lassegue - Emory UniversityQing Song - Morehouse School of MedicineBarry London - University of PittsburghSamuel C. Dudley - University of Illinois ChicagoHeather L. Bloom - Veterans Health AdministrationCharles D. Searles - Veterans Health AdministrationA. Maziar Zafari - Veterans Health Administration
- Resource Type
- Journal article
- Publication Details
- Journal of cardiac failure, Vol.18(9), pp.717-723
- DOI
- 10.1016/j.cardfail.2012.06.531
- PMID
- 22939041
- PMCID
- PMC3640363
- NLM abbreviation
- J Card Fail
- ISSN
- 1071-9164
- eISSN
- 1532-8414
- Publisher
- Elsevier
- Number of pages
- 7
- Grant note
- 101 BX000704 / VA Merit Review Award; US Department of Veterans Affairs T32HL007745 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) S21MD000101 / National Institute on Minority Health and Health Disparities; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD) T32HL007745 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01 / NHLBI grant Medtronic, Inc.; Medtronic NHLBI R01 Award HHSN268201000043C / NHLBI Program of Excellence in Nanotechnology
- Language
- English
- Date published
- 09/01/2012
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984297607002771
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