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(Circulation. 1996;94:236-239.)
© 1996 American Heart Association, Inc.

Articles

Angiotensin-Converting Enzyme Gene Polymorphism

What to Do About All the Confusion?

Donald R.J. Singer, MD, MRCP; Constantinos G. Missouris, MRCP; Steve Jeffery, PhD

the Clinical Pharmacology Unit, Department of Pharmacology and Clinical Pharmacology (D.R.J.S.), Blood Pressure Unit (C.G.M.), and Department of Medical Genetics (S.J.), St George's Hospital Medical School, London, England.

Correspondence to Dr D.R.J. Singer, Clinical Pharmacology Unit, Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 ORE England. E-mail d.singer@sghms.ac.uk.

Key Words: genetics • Editorials • angiotensin • cardiovascular diseases

	Introduction

 
There is great continuing interest in the link between a deletion variant of the gene for ACE and increased incidence of MI.¹ Although some studies^{2 3 4 5} have failed to confirm this finding, many^{6 7 8 9 10} have reported an association between the ACE*D allele and CHD, including several recent articles published in Circulation. Other positive associations with the ACE*D allele include restenosis after coronary angioplasty,⁶ cardiac hypertrophy and remodeling,^{11 12 13} ischemic or idiopathic dilated cardiomyopathy,¹⁴ hypertrophic cardiomyopathy,¹⁵ atheromatous renal artery stenosis,¹⁶ lacunar stroke,¹⁷ and diabetic nephropathy.¹⁸

Controversy Regarding ACE*D and Ischemic Heart Disease
The alu repeat is the most common family of repeats in the human genome. The insertion that gives rise to the ACE*I allele is an alu repeat in intron 16 of the ACE gene.¹⁹ The ACE*D allele results from the absence of the above insertion in the ACE gene. There is major disagreement about which individuals with the ACE*D allele are at greater risk of cardiovascular disease. The finding by Cambien et al¹ that classically low-risk individuals (low body mass index and low apolipoprotein B) are more likely to develop MI was not confirmed by Ludwig and colleagues⁸ or Mattu and colleagues.⁹ Although Mattu et al⁹ reported an association of the ACE*D allele with CHD in low-risk patients, this association was lost when the data were corrected for body mass index. Ludwig et al⁸ showed no such correlation but found that the ACE*D allele predicts MI. However, their sample size was only adequate to detect an odds ratio of >3.2 for an association between the ACE*D allele and . . . [Full Text of this Article]

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