Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Sep;18(9):717-23.
doi: 10.1016/j.cardfail.2012.06.531. Epub 2012 Aug 9.

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

Raul R Blanco  1 , Harland Austin, Richard N Vest 3rd, Ravinder Valadri, Wei Li, Bernard Lassegue, Qing Song, Barry London, Samuel C Dudley, Heather L Bloom, Charles D Searles, A Maziar Zafari
Affiliations

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

Raul R Blanco et al. J Card Fail. 2012 Sep.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Determination of ACE genotypes by PCR amplification
Representative agarose gel (1%, stained with ethidium bromide) containing PCR products. Lane 1 - negative control (NC); lanes 2, 5 and 6 - ID genotypes; lane 3 - II genotype; and lane 4 - DD genotype. This analysis was performed on the 485 subjects in the study.
Figure 2
Figure 2
Levels of miR-155 is whole blood of patients with 1166AA (n=25), 1166AC (n=21), and 1166CC (n=6) genotypes. Data shows the mean +/− SEM for qRT-PCR analysis of miR-155 (copy numbers) in RNA extracted from whole blood samples (PAXgene Blood RNA Tubes). Ct values were converted into copy numbers (copy# = 2(−Ct)) and normalized to RNU48. *p = 0.006, versus AA, Wilcoxon rank-sum test. A linear trend test across the 3 genotypes of the mean of the logarithm of miR-155 yields a p value of 0.002.
See this image and copyright information in PMC

References

    1. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation. 2001 Oct 30;104(18):2158–63. - PubMed
    1. Goldberger JJ, Cain ME, Hohnloser SH, Kadish AH, Knight BP, Lauer MS, et al. American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society scientific statement on noninvasive risk stratification techniques for identifying patients at risk for sudden cardiac death: a scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. Circulation. 2008 Sep 30;118(14):1497–518. - PubMed
    1. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. N Engl J Med. 1997 Nov 27;337(22):1576–83. - PubMed
    1. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005 Jan 20;352(3):225–37. - PubMed
    1. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002 Mar 21;346(12):877–83. - PubMed

Publication types