Left-Ventricular Structure and Function Are Influenced by Angiotensinogen Gene Polymorphism (−20 A/C) in Young Male Patients*

Background The activity of the renin-angiotensin system influences blood pressure (BP) and cardiovascular structure in humans. Therefore, we questioned whether left-ventricular (LV) structure and function are influenced by the −20 A/C variant of the angiotensinogen (AGT) gene in young normotensive or mildly hypertensive patients. Methods A homogenous cohort of young, male, white subjects ( n = 214) with normal or mildly elevated BP never treated in the past, or on current cardiovascular medication, were recruited. All subjects were genotyped by single-strand conformational polymorphism analysis and DNA sequencing for the −20 A/C polymorphism of the AGT gene. Ambulatory BP was assessed over 24 h by an automatic portable device. Left-ventricular structure and function were determined by two-dimensional guided M-mode echocardiography. Results The frequency of subjects homozygous for the −20 A allele was 73.4%, and the frequency for those with at least one copy of the −20 C allele was 26.6%. In hypertensive subjects with at least one copy of the −20 C allele, posterior ( P = .027) and septal ( P = .021) wall thickness, as well as LV mass ( P = .027), were greater than in hypertensive subjects homozygous for the −20 A allele. Moreover, LV functional parameters such as midwall fractional fiber shortenings ( P = .021) and the velocity of circumferential fiber shortening ( P = .013) were decreased in hypertensive subjects with at least one copy of the −20 C allele, compared with subjects homozygous for the −20 A allele. Confounding factors of LV structure and systolic function, such as age, height, body mass index, physical activity, ambulatory 24-h BP, and sodium intake, were similar between the −20 A/C variants of the AGT gene in both normotensive and hypertensive subjects. Conclusions In young, mildly hypertensive subjects, cardiac structure and function are modulated by the −20 A/C gene variant of the AGT.