title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Raul R
authors.initials: RR
authors.lastname: Blanco
authors.forename: Harland
authors.initials: H
authors.lastname: Austin
authors.forename: Richard N
authors.initials: RN
authors.lastname: Vest
authors.forename: Ravinder
authors.initials: R
authors.lastname: Valadri
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Bernard
authors.initials: B
authors.lastname: Lassegue
authors.forename: Qing
authors.initials: Q
authors.lastname: Song
authors.forename: Barry
authors.initials: B
authors.lastname: London
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Dudley
authors.forename: Heather L
authors.initials: HL
authors.lastname: Bloom
authors.forename: Charles D
authors.initials: CD
authors.lastname: Searles
authors.forename: A Maziar
authors.initials: AM
authors.lastname: Zafari
mesh_terms: D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016757:Death, Sudden, Cardiac / Q000473:pathology*; D017147:Defibrillators, Implantable; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012306:Risk; D013223:Statistics as Topic
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D044140:Receptor, Angiotensin, Type 1