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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Apr 26;91(9):3662–3665. doi: 10.1073/pnas.91.9.3662

Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus.

J Ruiz 1, H Blanché 1, N Cohen 1, G Velho 1, F Cambien 1, D Cohen 1, P Passa 1, P Froguel 1
PMCID: PMC43641  PMID: 8170965

Abstract

Non-insulin-dependent diabetes mellitus (NIDDM) is considered a model of premature atherosclerosis with a strong genetic component. We have investigated the role of angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene in 316 unrelated NIDDM individuals, 132 who had myocardial infarction or significant coronary stenoses and 184 with no history of coronary heart disease (CHD). A deletion-polymorphism in the ACE gene was recently reported to be associated with myocardial infarction especially in people classified as low risk. Here we report that the D allele of the ACE gene is a strong and independent risk factor for CHD in NIDDM patients. The D allele is associated with early-onset CHD in NIDDM, independently of hypertension and lipid values. A progressively increasing relative risk in individuals heterozygous and homozygous for the D allele was observed (odds ratios of 1.41 and 2.35, respectively; P < 0.007), suggesting a codominant effect on the cardiovascular risk. The percentage of CHD attributable to the ACE deletion allele was 24% in this NIDDM population. Identification of NIDDM patients carrying this putative CHD-susceptibility genotype would help early detection and treatment of CHD.

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Selected References

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  1. Cambien F., Poirier O., Lecerf L., Evans A., Cambou J. P., Arveiler D., Luc G., Bard J. M., Bara L., Ricard S. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992 Oct 15;359(6396):641–644. doi: 10.1038/359641a0. [DOI] [PubMed] [Google Scholar]
  2. Chatellier G., Lang T. Pathologie cardiovasculaire liée au vieillissement. Place de la prévention. Presse Med. 1992 Jul 22;21(26):1250–1255. [PubMed] [Google Scholar]
  3. Cox N. J., Bell G. I. Disease associations. Chance, artifact, or susceptibility genes? Diabetes. 1989 Aug;38(8):947–950. doi: 10.2337/diab.38.8.947. [DOI] [PubMed] [Google Scholar]
  4. Earle K., Walker J., Hill C., Viberti G. Familial clustering of cardiovascular disease in patients with insulin-dependent diabetes and nephropathy. N Engl J Med. 1992 Mar 5;326(10):673–677. doi: 10.1056/NEJM199203053261005. [DOI] [PubMed] [Google Scholar]
  5. Froguel P., Velho G., Cohen D., Passa P. Strategies for the collection of sibling-pair data for genetic studies in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1991 Sep;34(9):685–685. doi: 10.1007/BF00401001. [DOI] [PubMed] [Google Scholar]
  6. Hsueh W. A. Effect of the renin-angiotensin system in the vascular disease of type II diabetes mellitus. Am J Med. 1992 Apr 27;92(4B):13S–19S. doi: 10.1016/0002-9343(92)90142-x. [DOI] [PubMed] [Google Scholar]
  7. Laporte S., Escher E. Neointima formation after vascular injury is angiotensin II mediated. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1510–1516. doi: 10.1016/0006-291x(92)90473-x. [DOI] [PubMed] [Google Scholar]
  8. Naka M., Hiramatsu K., Aizawa T., Momose A., Yoshizawa K., Shigematsu S., Ishihara F., Niwa A., Yamada T. Silent myocardial ischemia in patients with non-insulin-dependent diabetes mellitus as judged by treadmill exercise testing and coronary angiography. Am Heart J. 1992 Jan;123(1):46–53. doi: 10.1016/0002-8703(92)90745-h. [DOI] [PubMed] [Google Scholar]
  9. Pfeffer M. A., Braunwald E., Moyé L. A., Basta L., Brown E. J., Jr, Cuddy T. E., Davis B. R., Geltman E. M., Goldman S., Flaker G. C. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992 Sep 3;327(10):669–677. doi: 10.1056/NEJM199209033271001. [DOI] [PubMed] [Google Scholar]
  10. Raynolds M. V., Bristow M. R., Bush E. W., Abraham W. T., Lowes B. D., Zisman L. S., Taft C. S., Perryman M. B. Angiotensin-converting enzyme DD genotype in patients with ischaemic or idiopathic dilated cardiomyopathy. Lancet. 1993 Oct 30;342(8879):1073–1075. doi: 10.1016/0140-6736(93)92061-w. [DOI] [PubMed] [Google Scholar]
  11. Reaven G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595–1607. doi: 10.2337/diab.37.12.1595. [DOI] [PubMed] [Google Scholar]
  12. Ridker P. M., Gaboury C. L., Conlin P. R., Seely E. W., Williams G. H., Vaughan D. E. Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function. Circulation. 1993 Jun;87(6):1969–1973. doi: 10.1161/01.cir.87.6.1969. [DOI] [PubMed] [Google Scholar]
  13. Rigat B., Hubert C., Alhenc-Gelas F., Cambien F., Corvol P., Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990 Oct;86(4):1343–1346. doi: 10.1172/JCI114844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rigat B., Hubert C., Corvol P., Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res. 1992 Mar 25;20(6):1433–1433. doi: 10.1093/nar/20.6.1433-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stamler J., Vaccaro O., Neaton J. D., Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993 Feb;16(2):434–444. doi: 10.2337/diacare.16.2.434. [DOI] [PubMed] [Google Scholar]
  16. Tiret L., Kee F., Poirier O., Nicaud V., Lecerf L., Evans A., Cambou J. P., Arveiler D., Luc G., Amouyel P. Deletion polymorphism in angiotensin-converting enzyme gene associated with parental history of myocardial infarction. Lancet. 1993 Apr 17;341(8851):991–992. doi: 10.1016/0140-6736(93)91075-w. [DOI] [PubMed] [Google Scholar]
  17. Viswanathan M., Strömberg C., Seltzer A., Saavedra J. M. Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta. J Clin Invest. 1992 Nov;90(5):1707–1712. doi: 10.1172/JCI116043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yusuf S., Pepine C. J., Garces C., Pouleur H., Salem D., Kostis J., Benedict C., Rousseau M., Bourassa M., Pitt B. Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions. Lancet. 1992 Nov 14;340(8829):1173–1178. doi: 10.1016/0140-6736(92)92889-n. [DOI] [PubMed] [Google Scholar]

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