The DD ACE gene polymorphism is associated with endothelial dysfunction in normal man

R. Butler*, A. D. Morris, B. Burchell, A. D. Struthers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: A polymorphism within the angiotensin converting enzyme (ACE) gene may increase the risk of myocardial infarction in individuals previously thought to be at low cardiovascular risk. The mechanism through which it exerts this effect is unknown, but may be due endothelial dysfunction. Methods and Results: We compared the endothelial function of the three genotypes (n= II=25 subjects, ID=31 subjects, DD=12 subjects) aged (mean±S.D) II 24±4, ID 25±6 and DD 25±6 years. The DD genotype was associated with a significant blunting in endothelial dependent vasodilatation (forearm blood flow data is presented as a mean ratio (± standard deviation) of blood flow in response to each vasoactive agent; the comparison is between DD vs. ID vs. II. The p value is an expression of an overall difference by ANOVA, the 95% confidence intervals are of a pairwise comparison between genotypes); acetylcholine 2.88±1.45 vs. 3.81±1.93 vs. 4.23±2.37 (p=0.002, 95% CI (II vs. ID) -0.19, 0.91, 95% CI (II vs. DD) 0.36, 1.80, 95% CI (ID vs. DD) 0.02, 1.42). There was also a significant difference with the endothelial independent vasodilator sodium nitroprusside 2.11±1.00 vs. 2.55±1.36 vs. 2.75±1.18 (p<0.05, 95% CI (II vs. ID) -0.15, 0.51, 95% CI (II vs. DD) 0.03, 0.89, 95% CI (ID vs. DD) -0.13, 0.71 ) but not with verapamil. There was no effect of the ACE genotype on endothelial dependent or independent vasoconstrictors monomethyl-L-arginine or norepinephrine. Investigating the effects of cigarette smoking on each genotype demonstrated that II and DD genotypes acetylcholine responses were further blunted if subjects smoked. Conclusion: These data demonstrate that the DD-ACE genotype in a young population is associated with a blunting of stimulated endothelial NO and donated NO responses, but not to non-NO vasodilators or vasoconstrictors.

Original languageEnglish
Issue numberSUPPL. 1
Publication statusPublished - 1 May 1999


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