An aldosterone synthase gene variant is associated with improvementin left ventricular ejection fraction in dilated cardiomyopathy

Abstract

Objective:To assess whether renin–angiotensin–aldosterone (RAA) system gene polymorphisms shown to be associated withalterations 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 idiopathicdilated cardiomyopathy (IDC) and class II–III heart failure was assessed. In 107 patients LVEF and LV dimensions were determined usingradionuclide ventriculography and echocardiography prior to and subsequent to receiving furosemide, digoxin and angiotensin-convertingenzyme (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:RAAsystem genotypes were not significantly associated with LVEF prior to initiating medical therapy. However, theCYP11B2gene variant(P50.0064 on covariate analysis [adjusted for multiple genotyping] with a 1–2% chance of false positive data), but neither the ACE, northe AGT variants, predicted improvement in LV ejection fraction in patients on medical therapy.Conclusion:ACYP11B2gene variantpredicts the variable improvement in LV ejection fraction that occurs subsequent to initiating medical therapy in IDC. These data suggest arole for the aldosterone synthase locus in regulating the progression of heart failure.