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

被引:44
作者
Blanco, Raul R. [2 ]
Austin, Harland [3 ]
Vest, Richard N., III [2 ,4 ]
Valadri, Ravinder [2 ]
Li, Wei [2 ]
Lassegue, Bernard [2 ]
Song, Qing [5 ]
London, Barry [6 ]
Dudley, Samuel C. [7 ]
Bloom, Heather L. [1 ,2 ]
Searles, Charles D. [1 ,2 ]
Zafari, A. Maziar [1 ,2 ]
机构
[1] Atlanta Vet Affairs Med Ctr, Decatur, GA 30033 USA
[2] Emory Univ, Sch Med, Atlanta, GA USA
[3] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA
[4] Med Univ S Carolina, Charleston, SC 29425 USA
[5] Morehouse Sch Med, Atlanta, GA 30310 USA
[6] Univ Pittsburgh, Pittsburgh, PA USA
[7] Univ Illinois, Chicago, IL USA
关键词
Genetic polymorphisms; angiotensin; angiotensin type 1 receptor; sudden cardiac death; heart failure; microRNA; SUDDEN CARDIAC DEATH; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; SIGNAL-TRANSDUCTION; CONVERTING ENZYME; MICRORNAS; EXPRESSION; DEFIBRILLATOR; MECHANISMS;
D O I
10.1016/j.cardfail.2012.06.531
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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)
引用
收藏
页码:717 / 723
页数:7
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