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 (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.
|Keywords||*Polymorphism, Genetic, Adult, Aged, Aged, 80 and over, Analysis of Variance, Biological Markers/blood, Cardiomyopathy, Hypertrophic/blood/*genetics, Enzyme Precursors/blood, Female, Genotype, Humans, Hypertrophy, Left Ventricular/blood/*genetics, Male, Middle Aged, Peptidyl-Dipeptidase A/*genetics, Receptor, Angiotensin, Type 1, Receptor, Angiotensin, Type 2, Receptors, Angiotensin/*genetics, Regression Analysis, Renin/blood, Research Support, Non-U.S. Gov't|
Osterop, A.P., Kofflard, M.J.M., Sandkuijl, L.A., Schalekamp, M.A.D.H., Danser, A.H.J., Krams, R., & ten Cate, F.J.. (1998). AT1 receptor A/C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy. Hypertension. Retrieved from http://hdl.handle.net/1765/8935