Angiotensin-converting enzyme and apolipoprotein E genotypes and restenosis after coronary angioplasty.
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.


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 (> or = 50% loss of gain at PTCA plus > or = 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 epsilon 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 epsilon 4 allele, but there was a significant effect in epsilon 4 carriers (P < .005). The combined D and epsilon 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 epsilon 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.
van Bockxmeer
F M
FM
Department of Biochemistry, Royal Perth (Australia) Hospital, Western Australia.
Mamotte
C D
CD
Gibbons
F A
FA
Burke
V
V
Taylor
R R
RR
D015906:Angioplasty, Balloon, Coronary; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011859:Radiography; D012008:Recurrence; D013997:Time Factors
D001057:Apolipoproteins E; D007703:Peptidyl-Dipeptidase A