(Hypertension. 1998;32:825-830.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
AT1 Receptor A/C1166 Polymorphism Contributes to Cardiac Hypertrophy in Subjects With Hypertrophic Cardiomyopathy
From the Departments of Internal Medicine I (A.P.R.M.O., M.A.D.H.S.), Cardiology (M.J.M.K., R.K., F.J.t.C.), Clinical Genetics (L.A.S.), and Pharmacology (A.H.J.D.), Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam, Erasmus University Rotterdam, Rotterdam, The Netherlands.
Correspondence to A.H.J. Danser, PhD, Department of Pharmacology, Room Ee1418B, Erasmus University Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, Netherlands. E-mail danser{at}farma.fgg.eur.nl
Abstract—The development of left ventricular hypertrophy (LVH) in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. We investigated whether the angiotensin II type 1 receptor (AT1-R) A/C1166 polymorphism, the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and/or plasma renin influence LVH in HCM. Left ventricular mass index (LVMI) and interventricular septal thickness were determined by 2-dimensional echocardiography in 104 genetically independent subjects with HCM. Extent of hypertrophy was quantified by a point score (Wigle score). Plasma prorenin, renin, and ACE were measured by immunoradiometric or fluorometric assays, and ACE and AT1-R genotyping were performed by polymerase chain reactions. The ACE D allele did not affect any of the measured parameters except plasma ACE (P<0.04). LVMI was higher (P<0.05) in patients carrying the AT1-R C allele (190±8.3 g/m2) than in AA homozygotes (168±7.2 g/m2), and similar patterns were observed for interventricular septal thickness (23.0±0.7 versus 21.6±0.7 mm) and Wigle score (7.0±0.3 versus 6.3±0.3). Plasma renin was higher (P=0.05) in carriers of the C allele than in AA homozygotes. Multivariate regression analysis, however, revealed no independent role for renin in the prediction of LVMI. Plasma prorenin and ACE were not affected by the AT1-R A/C1166 polymorphism, nor did the ACE and AT1-R polymorphisms interact with regard to any of the measured parameters. We conclude that the AT1-R C1166 allele modulates the phenotypic expression of hypertrophy in HCM, independently of plasma renin and the ACE I/D polymorphism.
Key Words: renin • cardiomyopathy • hypertrophy • receptors, angiotensin • angiotensin-converting enzyme
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