The insertion allele of the ACE gene I/D polymorphism. A candidate gene for insulin resistance?
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.


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.
Panahloo
A
A
Department of Medicine, University College London Medical School, Whittington Hospital, England.
Andrès
C
C
Mohamed-Ali
V
V
Gould
M M
MM
Talmud
P
P
Humphries
S E
SE
Yudkin
J S
JS
D000483:Alleles; D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics; D004251:DNA Transposable Elements; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D004251:DNA Transposable Elements; D017395:Plasminogen Activator Inhibitor 1; D007703:Peptidyl-Dipeptidase A