Clinical Studies
The Angiotensin II Type 1 Receptor Gene Polymorphism Is Associated With Coronary Artery Vasoconstriction☆

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Abstract

Objectives. This study sought to assess the potential association of the angiotensin-converting enzyme (ACE) and angiotensin II type 1 (AT1) receptor gene polymorphisms on coronary vasomotion in humans.

Background. Abnormal coronary vasomotion plays a role in the clinical expression of coronary atherosclerosis. The components of the renin–angiotensin system are important determinants of vasomotor tone. Furthermore, epidemiologic evidence suggests that these components are involved in the pathogenesis of coronary artery disease. Indeed, two genetic polymorphisms of the ACEand AT1receptor genes were synergistically associated with the occurrence of myocardial infarction. The influence of these genetic polymorphisms on the risk of myocardial infarction may be related, at least in part, to a deleterious effect on coronary vasomotion.

Methods. We studied the response of angiographically normal human coronary arteries after intravenous injection of methylergonovine maleate, a potent vasoconstrictor whose effects have been previously explored in various aspects of coronary artery disease. We characterized the ACEand AT1receptor genotypes in a consecutive series of 140 patients with normal coronary arteries. Coronary vasomotion was assessed with quantitative coronary angiography.

Results. No effect of the ACEgene polymorphism was detected. Conversely, the patients carrying the AT1receptor CCgenotype (n = 13) had significantly greater vasoconstriction in distal coronary vessels (p < 0.009).

Conclusions. The AT1receptor gene polymorphism is associated with coronary vasomotion in humans.

(J Am Coll Cardiol 1997;29:486–90)

Abbreviations

A/C
adenine/cytosine
ACE
angiotensin-converting enzyme
AT1
angiotensin II type 1 receptor
GLM
general linear models
I/D
insertion/deletion
ISDN
isosorbide dinitrate

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☆

Dr. Hamon was supported by a grant from the Société Française de Cardiologie, Paris, and Ms. Amant by the Conseil Régional du Nord-Pas de Calais, Lille, France. This work was supported by grants from the Direction de la Recherche et des Etudes Doctorales, Lille; the Centre Hospitalier Universitaire de Lille, Lille; the Institut National de la Santé et de la Recherche Médicale, Paris; and the Institut Pasteur de Lille, Lille, France.

Copyright © 1997 The American College of Cardiology. Published by Elsevier Inc. All rights reserved.