Effect of the angiotensin II type 2-receptor gene (+1675 G/A) on left ventricular structure in humans

OBJECTIVES Our study goal was to analyze whether gene variants of angiotens in II type 2-receptor (AT(2)-R) modulate the effects of angiotensin II on t he left ventricle (LV). BACKGROUND Experimental data suggest that angiotensin II modifies ventricul ar growth responses via angiotensin II type I-receptors (ATI-R) and AT2-R. METHODS In 120 white, young male subjects with normal or mildly elevated bl ood pressure, we assessed plasma angiotensin II and aldosterone concentrati ons (RIA), 24-h urinary sodium excretion, 24-h ambulatory blood pressure an d LV structure (two-dimensional guided M-mode echocardiography). The intron ic +1675 G/A polymorphism of the X-chromosomal located AT(2)-R gene was inv estigated by single-strand conformational polymorphism analysis and DNA-seq uencing. 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/ m(2), p < 0.001) than those with the G-allele. Confounding factors (i.e., b ody mass index and surface area, plasma angiotensin II, sodium excretion, s ystolic and diastolic ambulatory blood pressure) were similar between the t wo 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/m(2)) w ere nearly identical across the two genotypes, with similar confounding var iables. CONCLUSIONS Our data indicate that the X-chromosomal located + 1675 G/A-pol ymorphism of the AT(2)-R gene is associated with LV structure in young male humans with early structural changes of the heart due to arterial hyperten sion. (J Am Coil Cardiol 2001;37:175-82) (C) 2001 by the American College o f Cardiology.