AT1 receptor A/C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy

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 (AT(1)-R) A/C-1166 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 AT(1)-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 AT(1)-R C allele (190+/-8.3 g/m(2)) than in AA homozygotes (168+/-7.2 g/m(2)), 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 AT(1)-R A/C-1166 polymorphism, nor did the ACE and AT(1)-R polymorphisms interact with regard to any of the measured parameters. We conclude that the AT(1)-R C-1166 allele modulates the phenotypic expression of hypertrophy in HCM, independently of plasma renin and the ACE I/D polymorphism.