Association of Left Ventricular Mass With the AGTR1 A1166C Polymorphism

Yu Jin, Tatiana Kuznetsova, Lut Thijs, Boris Schmitz, Yanping Liu, Kei Asayama, Stefan-Martin Brand, Stephane Heymans, Eva Brand, Robert Fagard, Jan A. Staessen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Web of Science)

Abstract

BACKGROUND The A1166C polymorphism is located within the microRNA-155 binding site of the human angiotensin II (Ang II) type-1 receptor (AGTR1) gene. The C allele interferes with the base-pairing complementariness between AGTR1 mRNA and microRNA-155 and thereby increases AGTR1 protein expression in vitro. We hypothesized that left ventricular (LV) mass is associated with the AGTR1 A1166C polymorphism. METHODS Among 708 individuals (mean age, 49.4 years; 51.8% women) randomly recruited in a white European population, we measured LV structure by two-dimensional guided M-mode echocardiography, the AGTR1 A1166C polymorphism and the 24-h urinary aldosterone. We applied a mixed model to assess phenotype genotype associations while adjusting for covariables and accounting for relatedness. RESULTS The AA (49.1%), AC (42.8%), and CC (8.1%) genotypes were in Hardy-Weinberg equilibrium. Using a recessive model, CC homozygotes compared to A-allele carriers showed significant increases (P <0.021) in LV mass index (+5.78 +/- 2.25 g/m(2)), mean wall thickness (MWT) (+0.48 +/- 0.15 mm), interventricular septum (IVS) (+0.60 +/- 0.18 mm) and posterior wall thickness (PWT) (+0.34 +/- 0.15 mm), but lower 24-h urinary aldosterone excretion (geometric mean, 22.4 vs. 19.0 nmol; P = 0.050). Sensitivity analyses in 552 participants untreated for hypertension were confirmatory. CONCLUSIONS LV mass index is associated with the AGTR1 A1166C polymorphism. Further research should clarify to what extent this association might be mediated via different expression of AGTR1 as modulated by microRNA-155
Original languageEnglish
Pages (from-to)472-478
JournalAmerican Journal of Hypertension
Volume25
Issue number4
DOIs
Publication statusPublished - Apr 2012

Keywords

  • angiotensin II type 1 receptor
  • blood pressure
  • epidemiology
  • genetic association study
  • hypertension
  • left ventricular mass
  • microRNA

Cite this