The Insertion Allele of the ACE Gene I/D Polymorphism

Abstract

Background The insertion/deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased coronary heart disease (CHD), although the mechanism of this association is not apparent. We tested the hypothesis that the deletion allele of the ACE gene is associated with insulin resistance. Methods and Results We related ACE genotype to components of the insulin-resistance syndrome in 103 non–insulin-dependent diabetic (NIDDM) and 533 nondiabetic white subjects. NIDDM subjects with the DD genotype had significantly lower levels of specific insulin (DD 38.6, ID 57.1, and II 87.4 pmol · L −1 by ANOVA, P =.011). Non–insulin-treated subjects with the DD genotype had increased insulin sensitivity by HOMA % (DD 56.4%, II 29.4%, P =.027) and lower levels of des 31,32 proinsulin (DD 3.3, II 7.6 pmol · L −1 , P =.012) compared with II subjects. There were no differences in prevalence of CHD or levels of blood pressure, serum lipids, or plasminogen activator inhibitor–1 (PAI-1) activity between the three ACE genotypes. In nondiabetic subjects there were no differences in insulin sensitivity, levels of insulin-like molecules, blood pressure, PAI-1, serum lipids, or CHD prevalence between the three ACE genotypes. Conclusions We conclude that increased cardiovascular risk of the DD genotype is not mediated through insulin resistance or abnormalities in fibrinolysis. Conversely, we report an increased sensitivity in NIDDM subjects with the ACE DD genotype.

Insertion/Deletion Polymorphism of the ACE Gene Is Associated With Type 2 Diabetes

“…The D allele frequency was 40.2 and 32.8% in the case and the control groups, respectively, which is in line with previous reports of 29.3-41.6% frequencies in other Asian populations (5,10,11,13) and is much lower than the 52-57% frequencies reported in Caucasian populations (12,14,15). The observed genotype distribution was in Hardy-Weinberg equilibrium in control subjects ( 2 1 ϭ 0.03, P ϭ 0.96) and was marginally deviated from the equilibrium in case subjects ( 2 1 ϭ 3.77, P ϭ 0.05).…”

Association Between Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism and Risk of Rheumatic Heart Disease

“…23) However, I allele has also been shown to be associated with hypertension, insulin resistance, metabolic syndrome, mitral valve prolapse syndrome, and atrial fibrillation with hypertrophic cardiomyopathy. [24][25][26][27][28] The ACE II genotype can be a genetic risk factor for cardiovascular disease. The activity of renin is thought to be rate-limiting to the production of angiotensin II.…”

Exclusion of the ACE D/I Gene Polymorphism as a Determinant of Endothelial Dysfunction

“…The present finding of an increased endothelium-independent vasodilatation in subjects harboring the D allele is opposite to that previously reported in normotensive subjects 34 but consistent with previous reports of an association of the I allele with essential hypertension 53 and insulin resistance. 54 However, it is important to emphasize that this association was no longer significant after proper adjustment of FBF responses for the effects of age, serum glucose, and total plasma cholesterol, clearly indicating the crucial importance of control for the effect of confounding variables.…”