title: Genetic variation in angiotensin II type 2 receptor gene influences extent of left ventricular hypertrophy in hypertrophic cardiomyopathy independent of blood pressure.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM), an inherited primary cardiac disorder mostly caused by defective sarcomeric proteins, serves as a model to investigate left ventricular hypertrophy (LVH). HCM manifests extreme variability in the degree and distribution of LVH, even in patients with the same causal mutation. Genes coding for renin-angiotensin-aldosterone system components have been studied as hypertrophy modifiers in HCM, with emphasis on the angiotensin (Ang) II type 1 receptor (AT(1)R). However, Ang II binding to Ang II type 2 receptors (AT(2)R) also has hypertrophy-modulating effects.
  
  
  METHODS
  We investigated the effect of the functional +1675 G/A polymorphism (rs1403543) and additional single nucleotide polymorphisms in the 3' untranslated region of the AT(2)R gene (AGTR2) on a heritable composite hypertrophy score in an HCM family cohort in which HCM founder mutations segregate.
  
  
  RESULTS
  We find significant association between rs1403543 and hypertrophy, with each A allele decreasing the average wall thickness by ~0.5 mm, independent of the effects of the primary HCM causal mutation, blood pressure and other hypertrophy covariates (p = 0.020).
  
  
  CONCLUSIONS
  This study therefore confirms a hypertrophy-modulating effect for AT(2)R also in HCM and implies that +1675 G/A could potentially be used in a panel of markers that profile a genetic predisposition to LVH in HCM.
authors.affiliation: MRC Centre for Molecular and Cellular Biology, Department of Biomedical Sciences, University of Stellenbosch Health Sciences Faculty, Tygerberg, South Africa.
authors.forename: Nadia
authors.initials: N
authors.lastname: Carstens
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Miriam
authors.initials: M
authors.lastname: Revera
authors.forename: Marshall
authors.initials: M
authors.lastname: Heradien
authors.forename: Althea
authors.initials: A
authors.lastname: Goosen
authors.forename: Paul A
authors.initials: PA
authors.lastname: Brink
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Moolman-Smook
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*
chemical_list: D044139:Receptor, Angiotensin, Type 2