Association of angiotensin converting enzyme and angiotensin II type 1 receptor genotypes with left ventricular function and mass in patients with angiographically normal coronary arteries.

Abstract

Objective-To analyse the potential association of the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (ATIR) gene polymorphisms on left ventricular function and mass in patients with normal coronary arteries. Design-Consecutive sample. Setting-University hospital. Subjects-141 consecutive white patients referred for coronary angiography and with angiographically normal coronary arteries. Patients with valvar diseases, cardiomyopathies, or a history of myocardial infarction were excluded. Main outcome measures-Left ventricular variables were measured for all patients. The ACE and ATIR genotypes were determined with a polymerase chain reaction based protocol using DNA prepared from white blood cells. A general linear model was used to compare data according to the ACE and to the ATlR genotypes. Results-A strong association was observed between left ventricular mass and systemic hypertension (mean (SD) hypertension: 114 (31) g/m2; no hypertension 98 (23) glm2; P < 0.003). However, no influence of ACE and ATIR polymorphisms on left ventricular mass was found, regardless of systemic hypertension. The subjects homozygous for the ATIR CC mutation had a significantly lower ejection fraction than those with allele A (AC+AA) (mean (SD) 62(12)% and 68(10)%, respectively, P < 0.05). No synergistic interaction of ACE and ATlR gene polymorphisms on left ventricular function and mass was found. Conclusions-These data do not support an association of the ACE and ATIR genotypes on left ventricular hypertrophy in white patients with normal coronary arteries. (Heart 1997;77:502-505)

Lack of association between ACE gene polymorphism and left ventricular hypertrophy in essential hypertension

“…This lack of association found in our study is reinforced by the subgroup analysis of hypertensive patients included in general population studies. In fact, Lindpaintner et al, 4 Hamon et al 5 and Kupari et al 6 did not find any significant difference in LV mass among the three ACE genotypes, when the subset of hypertensives were analysed separately.…”

“…[7][8][9] Schunkert et al 3 first reported in 1994 a higher prevalence of the DD genotype in subjects with electrocardiographic evidence of LVH. However, three later studies [4][5][6] failed to confirm this association by assessing LVH by echocardiography. One of these studies, carried out by Lindpaintner et al 4 included a total of 2439 subjects from the Framingham population.…”

“…3,15 It has been demonstrated that the DD genotype of the ACE gene is accompanied by high plasma ACE activity, and it is believed that the resulting higher local concentrations of angiotensin II could promote inappropriate vascular wall thickening and myocardial hypertrophy. 2 Nevertheless, contradictory findings have been reported about the association of ACE gene polymorphism and LVH in both normotensive [3][4][5][6] and hypertensive populations. [7][8][9] Schunkert et al 3 first reported in 1994 a higher prevalence of the DD genotype in subjects with electrocardiographic evidence of LVH.…”

“…It has been suggested that essential hypertensives with this genotype may have an increased myocardial angiotensin II formation, leading to a greater degree of LVH. 2 Despite those data, contradictory findings have been reported about the ACE gene polymorphism and LVH in both normal [3][4][5][6] and hypertensive populations. [7][8][9] The aim of the present study was to evaluate the possible association between the I/D polymorphism of the ACE gene and the presence of LVH in a group of essential hypertensive patients.…”

Genes of renin angiotensin system and coronary heart disease

“…Their study indicated that the AT1 receptor polymorphism that may increase receptor number or sensitivity may not cause CVD directly but it can contribute to the process that is started by other factors such as high renin conditions. Although the above findings suggest a positive association between the ATl-receptor CC polymorphism and certain CVD, negative associations have also been reported in coronary atherosclerosis (45) and left ventricular hypertrophy (46). Recently Hilger et al (47) reported that NC 1166 polymorphism of AT1R does not affect high BP, renal hemodynamic and aldosterone response to infused All.…”