Association of Left Ventricular Mass With the AGTR1 A1166C Polymorphism

作者：Jin Yu; Kuznetsova Tatiana; Thijs Lut; Schmitz Boris; Liu Yanping; Asayama Kei; Brand Stefan Martin; Heymans Stephane; Brand Eva; Fagard Robert; Staessen Jan A^*

来源：American Journal of Hypertension, 2012, 25(4): 472-478.

DOI：10.1038/ajh.2011.244

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

BACKGROUND %26lt;br%26gt;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. %26lt;br%26gt;METHODS %26lt;br%26gt;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. %26lt;br%26gt;RESULTS %26lt;br%26gt;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 %26lt; 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. %26lt;br%26gt;CONCLUSIONS %26lt;br%26gt;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

• 出版日期2012-4