© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated cardiomyopathy
aCardiovascular Genomics and Heart Failure Research Units, Department of Physiology, Chris Hani-Baragwanath Hospital and the University of the Witwatersrand, Johannesburg, South Africa
bCardiovascular Genomics and Heart Failure Research Units, Department of Cardiology, Chris Hani-Baragwanath Hospital and the University of the Witwatersrand, Johannesburg, South Africa
cCardiovascular Genomics and Heart Failure Research Units, Department of Nuclear Cardiology, Chris Hani-Baragwanath Hospital and the University of the Witwatersrand, Johannesburg, South Africa
057nort{at}chiron.wits.ac.za
* Corresponding author. Cardiovascular Genomics and Heart Failure Research Units, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa. Tel.: +27-11-717-2363; fax: +27-11-717-2153
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.
KEYWORDS Cardiomyopathy; Heart failure; Sequence (DNA/RNA/prot)
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