Angiotensin-converting enzyme genotype is not associated with endothelial dysfunction in subjects without other coronary risk factors.
The DD genotype is a polymorphism of the angiotensin-converting enzyme (ACE) gene, and is associated with a significantly increased risk of myocardial infarction. As endothelial dysfunction is an important event in both early atherogenesis and late atherosclerosis, we hypothesised that the adverse effect associated with the ACE/DD genotype might be mediated via endothelial damage. Using high resolution ultrasound, we studied the brachial arteries of 184 subjects aged 15-73 (mean 38 +/- 14) years, who were all normotensive, non-diabetic lifelong non-smokers. Arterial diameter was measured at rest, during reactive hyperaemia (with flow increase causing endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN, an endothelium-independent vasodilator). The ACE genotype was determined in each case by DNA amplification; 49/184(27%) had DD, 89 (48%) had ID and 46 (25%) had II genotype. Flow-mediated dilation (FMD) was 8.5% +/- 3.9% in the DD, 7.8% +/- 4.1% in the ID and 7.8% +/- 4.1% in the II subjects (P = NS). GTN-induced dilation was also similar in the 3 groups. On multivariate analysis, endothelium-dependent dilation was inversely related to age (r = -0.33, P < 0.001), vessel size (r = -0.41, P < 0.001) but not ACE genotype (r = 0.002, P = 0.97). The ACE genotype is unrelated to endothelium-dependent dilation in the systemic arteries of clinically well adults. This suggests that the risk associated with this polymorphism may be mediated by other mechanisms.
Celermajer
D S
DS
Cardiothoracic Unit, Hospital for Sick Children, London, UK.
Sorensen
K E
KE
Barley
J
J
Jeffrey
S
S
Carter
N
N
Deanfield
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000503:physiopathology; D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D005838:Genotype; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects
D007703:Peptidyl-Dipeptidase A; D005996:Nitroglycerin