Increased risk for ischaemic events is related to combined RAS polymorphism

Abstract

Objective-To determine whether the angiotensin converting enzyme (ACE) and the angiotensin II type 1 receptor (AT 1 R A1166C) gene polymorphism interact to increase the risk of ischaemic events, and whether this can be explained by the progression of angiographically defined coronary atherosclerosis. Design-Prospective defined substudy of the lipid lowering regression trial (REGRESS). Setting-University hospital. Patients-885 male patients with stable coronary artery disease. Main outcome measures-Incidence of ischaemic events during a two year follow up; serial quantitative coronary arteriography (mean segment diameter and minimum obstruction diameter) at baseline and after two years. Results-Patients who carried both the ACE-DD and AT 1 R-CC genotype had significantly more ischaemic events during the two year follow up than those carrying other genotype combinations (p = 0.035, Mantel-Haenszel test for linear association). There was no association between the two genotypes and mean segment diameter or minimum obstruction diameter at baseline or after two years. Conclusions-The suggestion that ACE-DD and AT 1 R-CC genotypes interact to increase the risk of ischaemic events is confirmed. However, this increased risk was not accompanied by increased progression of angiographically defined coronary atherosclerosis. (Heart 2001;85:458-462)

Genotypic interactions of renin–angiotensin system genes in myocardial infarction

“…Ludwig et al [16] and Fomicheva et al [17] observed a significant interaction between the AGT and ACE genes. Tiret et al [33] and van Geel et al [34] found a significant association between ACE and AGTR1, and Á lvarez et al [35] have demonstrated an interaction between AGT and AGTR1. These results strengthen the hypothesis that genotypic combinations are more important than single gene polymorphism alone.…”

Influence of Renin Angiotensin System Gene Polymorphisms on Visit-to-Visit Blood Pressure Variability in Hypertensive Patients

“…22 Similarly, AT1R A1166C reportedly correlates with CVD, including increased left ventricular mass index 16 and diabetic nephropathy. 32 Previous cohort studies have also shown that AT1R A1166C significantly correlates with the frequency of restenosis following coronary artery angioplasty, 33 incidence of CVD and mortality, 34 and myocardial infarction. 35 Several studies have indicated that these polymorphisms significantly correlated with CVD or prognosis; however, little is known about how RAS gene polymorphisms affect the onset of CVD or prognosis in clinical setting.…”

Molecular genetics of atherosclerosis

“…A meta-analysis of 46 studies including a total of 32,715 Caucasian subjects concluded that the insertiondeletion polymorphism in ACE gene was not associated with increased risk of MI, CAD, or ischemic cerebrovascular disease (Agerholm-Larsen et al 2000). It has been suggested that a combination of genotype variants of the renin-angiotensin system genes could be a signiWcant determinant of ischemic events (van Geel et al 2001) and CAD (Kretowski et al 2007).…”