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.