Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction

Abstract

Background: The angiotensin-converting enzyme (ACE) plays an important role in the production of angiotensin II and the degradation of bradykinin, two peptides involved in cardiovascular homeostasy. Presence of a polymorphism in the ACE gene (ACE Ss) has been postulated from segregation analysis of plasma ACE in families. This putative polymorphism, which strongly affects the plasma and cellular levels of ACE, probably by modulating ACE gene transcription, has not yet been identified at the molecular level; however, an insertion/deletion polymorphism is present in the 16th intron of the ACE gene (ACE I/D) and appears to be a very good marker for ACE Ss. The biological role of ACE suggests that the ACE gene polymorphism could affect the predisposition to myocardial infarction (MI). Methods and Results: We have recently shown, in a large case-control study (ECTIM), that the marker allele D of the ACE gene, which is associated with higher levels of ACE in plasma and cells, was more frequent in male patients with MI than in control subjects, especially in patients considered at low risk. ACE activity has now been measured from frozen aliquots of plasma in a large subsample of the ECTIM study (n=1086). Plasma ACE level did not differ between patients and control subjects in the older age group (≥55 years) but was higher in patients than in control subjects in the younger age group (<55 years); P <10-4), but in control subjects no such trend was observed. In the low-risk group (ApoB <1.25 mg/dL, body mass index <26 kg/m2, and not treated with hypolipidemic drugs), plasma ACE level was increased in patients when compared with control subjects among homozygotes and heterozygotes for the ACE I allele (P