Effect of the angiotensin II type 2-receptor gene (+1675 G/A) on left ventricular structure in humans.
OBJECTIVE
Our study goal was to analyze whether gene variants of angiotensin II type 2-receptor (AT2-R) modulate the effects of angiotensin II on the left ventricle (LV).


BACKGROUND
Experimental data suggest that angiotensin II modifies ventricular growth responses via angiotensin II type 1-receptors (AT1-R) and AT2-R.


METHODS
In 120 white, young male subjects with normal or mildly elevated blood pressure, we assessed plasma angiotensin II and aldosterone concentrations (RIA), 24-h urinary sodium excretion, 24-h ambulatory blood pressure and LV structure (two-dimensional guided M-mode echocardiography). The intronic +1675 G/A polymorphism of the X-chromosomal located AT2-R gene was investigated by single-strand conformational polymorphism analysis and DNA-sequencing.


RESULTS
Hypertensive subjects with the A-allele had a greater LV posterior (11.0 +/- 1.3 vs. 9.9 +/- 1.3 mm, p < 0.001), septal (11.8 +/- 1.4 vs. 10.1 +/- 1.2 mm, p < 0.001) and relative wall thickness (0.44 +/- 0.06 vs. 0.39 +/- 0.06, p < 0.01) as well as LV mass index (138 +/- 23 vs. 120 +/- 13 g/m2, p < 0.001) than those with the G-allele. Confounding factors (i.e., body mass index and surface area, plasma angiotensin II, sodium excretion, systolic and diastolic ambulatory blood pressure) were similar between the two genotypes. In normotensive subjects, relative wall thickness (0.36 +/- 0.05 vs. 0.35 +/- 0.05) and LV mass index (115 +/- 21 vs. 112 +/- 17 g/m2) were nearly identical across the two genotypes, with similar confounding variables.


CONCLUSIONS
Our data indicate that the X-chromosomal located +1675 G/A-polymorphism of the AT2-R gene is associated with LV structure in young male humans with early structural changes of the heart due to arterial hypertension.
Schmieder
R E
RE
Department of Medicine IV/Nephrology, University of Erlangen-Nürnberg, Germany. Roland.Schmieder@rzmail.uni-erlangen.de
Erdmann
J
J
Delles
C
C
Jacobi
J
J
Fleck
E
E
Hilgers
K
K
Regitz-Zagrosek
V
V
D000328:Adult; D000483:Alleles; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D014960:X Chromosome
D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin