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.

CONCLUSION:

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: Armindo D Tiago, Danelle Badenhorst, Daniel Skudicky, Angela J Woodiwiss, Geoffrey P Candy, Richard Brooksbank, Karen Sliwa, Pinhas Sareli, Gavin R Norton
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 54 Issue 3 Pg. 584-9 (Jun 2002) ISSN: 0008-6363 [Print] England
• PMID: 12031704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Diuretics
• Enzyme Inhibitors
• Angiotensinogen
• Digoxin
• Furosemide
• Cytochrome P-450 CYP11B2
• Peptidyl-Dipeptidase A

Topics

• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Angiotensinogen (genetics)
• Cardiomyopathy, Dilated (enzymology, pathology, physiopathology)
• Case-Control Studies
• Cytochrome P-450 CYP11B2 (genetics)
• Digoxin (therapeutic use)
• Diuretics (therapeutic use)
• Echocardiography
• Enzyme Inhibitors (therapeutic use)
• Female
• Furosemide (therapeutic use)
• Heart Ventricles (pathology)
• Humans
• Logistic Models
• Male
• Middle Aged
• Peptidyl-Dipeptidase A (genetics)
• Polymorphism, Genetic
• Radionuclide Ventriculography
• Stroke Volume