title: AT1 receptor A/C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy.
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.
authors.affiliation: Departments of Internal Medicine I, Cardiology, Clinical Genetics, and Pharmacology, Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam, The Netherlands.
authors.forename: A P
authors.initials: AP
authors.lastname: Osterop
authors.forename: M J
authors.initials: MJ
authors.lastname: Kofflard
authors.forename: L A
authors.initials: LA
authors.lastname: Sandkuijl
authors.forename: F J
authors.initials: FJ
authors.lastname: ten Cate
authors.forename: R
authors.initials: R
authors.lastname: Krams
authors.forename: M A
authors.initials: MA
authors.lastname: Schalekamp
authors.forename: A H
authors.initials: AH
authors.lastname: Danser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000235:genetics*; D004792:Enzyme Precursors / Q000097:blood; D005260:Female; D005838:Genotype; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D012044:Regression Analysis; D012083:Renin / Q000097:blood
chemical_list: D015415:Biomarkers; D004792:Enzyme Precursors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D007703:Peptidyl-Dipeptidase A; D012083:Renin