title: An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated cardiomyopathy.
abstract: OBJECTIVE
  To assess whether renin-angiotensin-aldosterone (RAA) system gene polymorphisms shown to be associated with alterations in the activity of the system, may predict cardiac function changes subsequent to initiating medical therapy in heart failure.
  
  
  METHODS
  The impact of RAA system genotypes on left ventricular ejection fraction (LVEF) following therapy to patients with idiopathic dilated cardiomyopathy (IDC) and class II-III heart failure was assessed. In 107 patients LVEF and LV dimensions were determined using radionuclide ventriculography and echocardiography prior to and subsequent to receiving furosemide, digoxin and angiotensin-converting enzyme (ACE) inhibitor therapy. Patients and controls were genotyped for variants of the ACE (insertion-deletion polymorphism), angiotensinogen (AGT; M235T polymorphism) and the aldosterone synthase (CYP11B2, C-344T polymorphism) genes.
  
  
  RESULTS
  RAA system genotypes were not significantly associated with LVEF prior to initiating medical therapy. However, the CYP11B2 gene variant (P=0.0064 on covariate analysis [adjusted for multiple genotyping] with a 1-2% chance of false positive data), but neither the ACE, nor the AGT variants, predicted improvement in LV ejection fraction in patients on medical therapy.
  
  
  CONCLUSIONS
  A CYP11B2 gene variant predicts the variable improvement in LV ejection fraction that occurs subsequent to initiating medical therapy in IDC. These data suggest a role for the aldosterone synthase locus in regulating the progression of heart failure.
authors.affiliation: Cardiovascular Genomics and Heart Failure Research Units, Department of Physiology, Chris Hani-Baragwanath Hospital and the University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Armindo D
authors.initials: AD
authors.lastname: Tiago
authors.forename: Danelle
authors.initials: D
authors.lastname: Badenhorst
authors.forename: Daniel
authors.initials: D
authors.lastname: Skudicky
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Woodiwiss
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Candy
authors.forename: Richard
authors.initials: R
authors.lastname: Brooksbank
authors.forename: Karen
authors.initials: K
authors.lastname: Sliwa
authors.forename: Pinhas
authors.initials: P
authors.lastname: Sareli
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Norton
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000808:Angiotensinogen / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D004077:Digoxin / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004452:Echocardiography; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D015635:Radionuclide Ventriculography; D013318:Stroke Volume
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D004791:Enzyme Inhibitors; D000808:Angiotensinogen; D004077:Digoxin; D005665:Furosemide; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A