TY - JOUR
T1 - Association of Left Ventricular Mass With the AGTR1 A1166C Polymorphism
AU - Jin, Yu
AU - Kuznetsova, Tatiana
AU - Thijs, Lut
AU - Schmitz, Boris
AU - Liu, Yanping
AU - Asayama, Kei
AU - Brand, Stefan-Martin
AU - Heymans, Stephane
AU - Brand, Eva
AU - Fagard, Robert
AU - Staessen, Jan A.
PY - 2012/4
Y1 - 2012/4
N2 - 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
AB - 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
KW - angiotensin II type 1 receptor
KW - blood pressure
KW - epidemiology
KW - genetic association study
KW - hypertension
KW - left ventricular mass
KW - microRNA
U2 - 10.1038/ajh.2011.244
DO - 10.1038/ajh.2011.244
M3 - Article
C2 - 22237156
SN - 0895-7061
VL - 25
SP - 472
EP - 478
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 4
ER -