Genetic variation in angiotensin II type 2 receptor gene influences extent of left ventricular hypertrophy in hypertrophic cardiomyopathy independent of blood pressure

Nadia Carstens, Lize Van Der Merwe, Miriam Revera, Marshall Heradien, Althea Goosen, Paul A. Brink, Johanna C. Moolman-Smook

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction. 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 1R). However, Ang II binding to Ang II type 2 receptors (AT 2R) 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 2R 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). Conclusion. This study therefore confirms a hypertrophy-modulating effect for AT 2R 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.

Original languageEnglish
Pages (from-to)274-280
Number of pages7
JournalJRAAS - Journal of the Renin-Angiotensin-Aldosterone System
Volume12
Issue number3
DOIs
Publication statusPublished - Sep 2011

Keywords

  • Angiotensin II type 2 receptor
  • cardiac hypertrophy
  • hypertrophic cardiomyopathy
  • renin-angiotensin-aldosterone system

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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