(Circulation. 1995;92:2066-2071.)
© 1995 American Heart Association, Inc.
Articles |
Angiotensin-Converting Enzyme and Apolipoprotein E Genotypes and Restenosis After Coronary Angioplasty
From the Department of Biochemistry (F.M. van B., C.D.S.M.), Department of Cardiology (F.A.G., R.R.T.), and University Department of Medicine (R.R.T., V.B.), Royal Perth (Australia) Hospital.
Correspondence to Frank M. van Bockxmeer, PhD, Department of Biochemistry, Royal Perth Hospital, Wellington Street, Perth, Western Australia 6000.
Background An insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) has been associated with myocardial infarction and other cardiac pathology. There is evidence for a role of the renin-angiotensin system in cell growth and in the repair of damaged arterial walls, so the ACE gene was postulated to be a candidate gene affecting the important clinical problem of restenosis after percutaneous transluminal balloon coronary angioplasty (PTCA). Because restenosis is influenced by the apolipoprotein E (apoE) genotype, the possibility of a relation between ACE and apoE genotypes and restenosis was also sought.
Methods and Results Subjects (<70 years of age) were
prospectively followed and had coronary angiography 6 months
after PTCA to determine the presence or absence of
restenosis. Those who had angiography earlier and did not
have restenosis (
50% loss of gain at PTCA plus 50%
luminal diameter stenosis) also had angiography at 6 months.
The whole group (n=207) had a higher DD genotype
frequency than did 136 population control subjects (38% versus 26%,
P<.02); in PTCA patients, the frequency was the same in
those with and without prior myocardial infarction. The distribution of
ACE genotypes was not different in the 88 patients with and 119
patients without restenosis, while the 
4/4
genotype was more frequent in those with restenosis
(8 of 88 versus 3 of 118, P<.05). There was no effect of
the ACE genotype in noncarriers of the 4 allele, but
there was a significant effect in 4 carriers (P<.005).
The combined D and 4 carrier state showed a 16-fold
increase in the odds ratio for restenosis
(P<.02). Multiple linear regression examining the loss of
lumen as a continuous variable showed significant independent
effects of the ACE and apoE genotypes.
Conclusions Overall, the ACE genotype had no clear
influence on restenosis, but there was an interaction
between ACE and apoE genotypes. The combined carrier state for
the D and apoE 4 alleles substantially increased
restenosis. For loss of lumen as a continuous variable,
there were significant effects of both ACE and apoE genotypes.
While the observations may not affect current management, they no doubt
have implications in pathophysiology.
Key Words: genes • restenosis • apolipoproteins • angiotensin
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