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.
Cardiothoracic Unit, Hospital for Sick Children, London, UK.
D S
DS
Celermajer
K E
KE
Sorensen
J
J
Barley
S
S
Jeffrey
N
N
Carter
J
J
Deanfield
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