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THE INSERTION ALLELE OF THE ACE GENE I/D POLYMORPHISM - A CANDIDATE GENE FOR INSULIN-RESISTANCE

PANAHLOO, A; ANDRES, C; MOHAMEDALI, V; GOULD, MM; TALMUD, P; HUMPHRIES, SE; YUDKIN, JS; (1995) THE INSERTION ALLELE OF THE ACE GENE I/D POLYMORPHISM - A CANDIDATE GENE FOR INSULIN-RESISTANCE. CIRCULATION , 92 (12) 3390 - 3393.

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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.

Type:Article
Title:THE INSERTION ALLELE OF THE ACE GENE I/D POLYMORPHISM - A CANDIDATE GENE FOR INSULIN-RESISTANCE
Keywords:INSULIN RESISTANCE, ANGIOTENSIN, ACE GENE, PLASMINOGEN ACTIVATOR INHIBITOR, DELETION POLYMORPHISM, MYOCARDIAL-INFARCTION, CONVERTING ENZYME, ANGIOTENSIN-II, GLUCOSE, PLASMA, SYSTEM
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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