The angiotensin II type 1 receptor gene polymorphism is associated with coronary artery vasoconstriction.
OBJECTIVE
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 ACE and AT1 receptor 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 ACE and AT1 receptor 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 ACE gene polymorphism was detected. Conversely, the patients carrying the AT1 receptor CC genotype (n = 13) had significantly greater vasoconstriction in distal coronary vessels (p < 0.009).


CONCLUSIONS
The AT1 receptor gene polymorphism is associated with coronary vasomotion in humans.
Amant
C
C
CJF INSERM 95-05, Institut Pasteur de Lille, France.
Hamon
M
M
Bauters
C
C
Richard
F
F
Helbecque
N
N
McFadden
E P
EP
Escudero
X
X
Lablanche
J M
JM
Amouyel
P
P
Bertrand
M E
ME
D000328:Adult; D000804:Angiotensin II / Q000235:genetics; D003331:Coronary Vessels / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007548:Isosorbide Dinitrate; D008297:Male; D008755:Methylergonovine / Q000494:pharmacology; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011945:Receptors, Angiotensin / Q000235:genetics*; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology
D011945:Receptors, Angiotensin; D014665:Vasodilator Agents; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D007548:Isosorbide Dinitrate; D008755:Methylergonovine