Angiotensin-Converting Enzyme and Apolipoprotein E Genotypes and Restenosis After Coronary Angioplasty

Publisher Website
Google Scholar
Abstract
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 (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 ε4/4 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 ε4 allele, but there was a significant effect in ε4 carriers ( P <.005). The combined D and ε4 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 ε4 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.