AT(1) RECEPTOR A C-1166 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 an giotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphis m, and/or plasma renin influence LVH in HCM. Left ventricular mass ind ex (LVMI) and interventricular septal thickness were determined by 2-d imensional echocardiography in 104 genetically independent subjects wi th HCM. Extent of hypertrophy was quantified by a point score (Wigle s core). Plasma prorenin, renin, and ACE were measured by immunoradiomet ric or fluorometric assays, and ACE and AT(1)-R genotyping were perfor med by polymerase chain reactions. The ACE D allele did not affect any of the measured parameters except plasma ACE (P<0.04). LVMI was highe r (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 homozygote s. 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 an d AT(1)-R polymorphisms interact with regard to any of the measured pa rameters. We conclude that the AT(1)-R C-1166 allele modulates the phe notypic expression of hypertrophy in HCM, independently of plasma reni n and the ACE I/D polymorphism.