Angiotensin-Converting Enzyme and Angiotensinogen Gene Polymorphisms, Plasma Levels, Cardiac Dimensions A Twin Study

Abstract

We tested the hypotheses that angiotensin-converting enzyme insertion/deletion (I/D) and angiotensinogen 235 methionine/threonine (M/T) substitution gene polymorphisms influence angiotensin-converting enzyme and angiotensinogen serum concentrations and cardiac dimensions in 91 monozygotic and 41 dizygotic twin pairs. Cardiac dimensions were determined echo-cardiographically. Angiotensin-converting enzyme levels were 24±11, 43±18, and 58±24 U/L for the II, ID, and DD genotypes, respectively ( P <.01). Posterior wall thickness was 8.1±1.3, 8.6±1.7, and 8.9±1.9 mm for these genotypes ( P <.05). Angiotensin-converting enzyme levels were correlated with posterior wall thickness ( r =.15, P <.05). The intrapair differences in angiotensin converting enzyme levels for monozygotic, concordant dizygotic, and discordant dizygotic twins were 1.36±1.6, 1.86±1.6, and 17.25±4.3 U/L, respectively. The angiotensinogen M/T genotypes exerted no influence on cardiac dimensions or on angiotensinogen concentrations. The additive genetic effect on angiotensin-converting enzyme levels (0.49), on posterior wall thickness (0.26), and on septum thickness (0.37) was significant ( P <.01), although shared and nonshared environmental effects were also identified. Our data confirm the impressive effect that the angiotensin-converting enzyme D allele exerts on angiotensin-converting enzyme plasma levels. Furthermore, our data also suggest that the angiotensin-converting enzyme gene locus is primarily responsible for angiotensin-converting enzyme plasma levels. Our twin study also indicates that the angiotensin-converting enzyme gene locus is genetically linked to posterior wall thickness. The correlation between angiotensin-converting enzyme levels and posterior wall thickness suggests that this effect is exerted by angiotensin-converting enzyme. We were unable to demonstrate genetic linkage between the angiotensinogen gene locus and cardiac dimensions in this study.