(Circulation. 1995;92:3390-3393.)
© 1995 American Heart Association, Inc.
Articles |
The Insertion Allele of the ACE Gene I/D Polymorphism
A Candidate Gene for Insulin Resistance?
From the Departments of Medicine (A.P., C.A., V.M.-A., J.S.Y.) and Primary Health Care (M.M.G.), University College London Medical School, Whittington Hospital, Archway Road, London, and Division of Cardiovascular Genetics (P.T., S.E.H.), Department of Medicine, University College London Medical School, Rayne Institute, University Street, London, England.
Correspondence to Dr A. Panahloo, Department of Medicine, University College London Medical School, Whittington Hospital, Archway Road, London N19 3UA England.
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.
Key Words: insulin resistance • angiotensin • ACE gene • plasminogen activator inhibitor
This article has been cited by other articles:
 |
|
 |
|
  E. Zintzaras, G. Raman, G. Kitsios, and J. Lau Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphic Variant as a Marker of Coronary Artery Disease: A Meta-analysis Arch Intern Med, May 26, 2008; 168(10): 1077 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J Milionis, M. S Kostapanos, K. Vakalis, I. Theodorou, I. Bouba, R. Kalaitzidis, I. Georgiou, M. S Elisaf, and K. C Siamopoulos Impact of renin-angiotensin-aldosterone system genes on the treatment response of patients with hypertension and metabolic syndrome Journal of Renin-Angiotensin-Aldosterone System, December 1, 2007; 8(4): 181 - 189. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Muthumala, H. Montgomery, J. Palmen, J. A. Cooper, and S. E. Humphries Angiotensin-Converting Enzyme Genotype Interacts With Systolic Blood Pressure to Determine Coronary Heart Disease Risk in Healthy Middle-Aged Men Hypertension, August 1, 2007; 50(2): 348 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Han, X. Wang, Y. Cui, H. Ye, X. Tong, and M. Piao Relationship Between Angiotensin-Converting Enzyme Gene Insertion or Deletion Polymorphism and Insulin Sensitivity in Healthy Newborns Pediatrics, June 1, 2007; 119(6): 1089 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Orchard, T. Costacou, A. Kretowski, and R. W. Nesto Type 1 diabetes and coronary artery disease. Diabetes Care, November 1, 2006; 29(11): 2528 - 2538. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Costacou, Y. Chang, R. E. Ferrell, and T. J. Orchard Identifying Genetic Susceptibilities to Diabetes-related Complications among Individuals at Low Risk of Complications: An Application of Tree-Structured Survival Analysis Am. J. Epidemiol., November 1, 2006; 164(9): 862 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Heimann, M. H. Favarato, F. C. Gozzo, V. Rioli, F. R. Carreno, M. N. Eberlin, E. S. Ferro, J. H. Krege, and J. E. Krieger ACE gene titration in mice uncovers a new mechanism for ACE on the control of body weight Physiol Genomics, January 20, 2005; 20(2): 173 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden American Association of Clinical Endocrinologists (AACE) Consensus Conference on the Insulin Resistance Syndrome: 25-26 August 2002, Washington, DC Diabetes Care, March 1, 2003; 26(3): 933 - 939. [Full Text] [PDF]
|
|
|
|
|
|
C.-T. Tsai, D. Fallin, F.-T. Chiang, J.-J. Hwang, L.-P. Lai, K.-L. Hsu, C.-D. Tseng, C.-S. Liau, and Y.-Z. Tseng Angiotensinogen Gene Haplotype and Hypertension: Interaction With ACE Gene I Allele Hypertension, January 1, 2003; 41(1): 9 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Feng, T. Niu, X. Xu, C. Chen, Q. Li, R. Qian, G. Wang, and X. Xu Insertion/Deletion Polymorphism of the ACE Gene Is Associated With Type 2 Diabetes Diabetes, June 1, 2002; 51(6): 1986 - 1988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Hurlbut, M. E. Lott, A. S. Ryan, R. E. Ferrell, S. M. Roth, F. M. Ivey, G. F. Martel, J. T. Lemmer, J. L. Fleg, and B. F. Hurley Does age, sex, or ACE genotype affect glucose and insulin responses to strength training? J Appl Physiol, February 1, 2002; 92(2): 643 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Ryan, B. J. Nicklas, D. M. Berman, and R. E. Ferrell The Insertion/Deletion Polymorphism of the ACE Gene Is Related to Insulin Sensitivity in Overweight Women Diabetes Care, September 1, 2001; 24(9): 1646 - 1652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. N. Thomas, B. Tomlinson, J. C.N. Chan, J. E. Sanderson, C. S. Cockram, and J. A.J.H. Critchley Renin-Angiotensin System Gene Polymorphisms, Blood Pressure, Dyslipidemia, and Diabetes in Hong Kong Chinese: A significant association of the ACE insertion/deletion polymorphism with type 2 diabetes Diabetes Care, February 1, 2001; 24(2): 356 - 361. [Abstract] [Full Text]
|
|
|
|
|
|
G. P. Rossi, S. Taddei, A. Virdis, L. Ghiadoni, G. Albertin, S. Favilla, I. Sudano, A. C. Pessina, and A. Salvetti Exclusion of the ACE D/I Gene Polymorphism as a Determinant of Endothelial Dysfunction Hypertension, February 1, 2001; 37(2): 293 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Perticone, R. Ceravolo, S. Iacopino, C. Cloro, G. Ventura, R. Maio, E. Gulletta, N. Perrotti, and P. L. Mattioli Relationship between Angiotensin-Converting Enzyme Gene Polymorphism and Insulin Resistance in Never-Treated Hypertensive Patients J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 172 - 178. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Cesari and G. P. Rossi Plasminogen Activator Inhibitor Type 1 in Ischemic Cardiomyopathy Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1378 - 1386. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kario, T. Matsuo, H. Kobayashi, N. Kanai, S. Hoshide, T. Mitsuhashi, U. Ikeda, S. Nishiuma, M. Matsuo, and K. Shimada Endothelial cell damage and angiotensin-converting enzyme insertion/deletion genotype in elderly hypertensive patients J. Am. Coll. Cardiol., August 1, 1998; 32(2): 444 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Margaglione, G. Cappucci, M. d'Addedda, D. Colaizzo, N. Giuliani, G. Vecchione, G. Mascolo, E. Grandone, and G. Di Minno PAI-1 Plasma Levels in a General Population Without Clinical Evidence of Atherosclerosis : Relation to Environmental and Genetic Determinants Arterioscler Thromb Vasc Biol, April 1, 1998; 18(4): 562 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-K. Kim, J.-W. Kim, S. Kim, H.-C. Gwon, J.-C. Ryu, J.-E. Huh, J.-A Choo, Y. Choi, C.-H. Rhee, and W.-R. Lee Polymorphism of Angiotensin Converting Enzyme Gene Is Associated With Circulating Levels of Plasminogen Activator Inhibitor-1 Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3242 - 3247. [Abstract] [Full Text]
|
|