PLASMA-LEVEL AND GENE POLYMORPHISM OF ANGIOTENSIN-CONVERTING ENZYME IN RELATION TO MYOCARDIAL-INFARCTION

Background The angiotensin-converting enzyme (ACE) plays an important role in the production of angiotensin II and the degradation of bradyk inin, two peptides involved in cardiovascular homeostasy. Presence of a polymorphism in the ACE gene (ACE Ss) has been postulated from segre gation analysis of plasma ACE in families. This putative polymorphism, which strongly affects the plasma and cellular levels of ACE, probabl y by modulating ACE gene transcription, has not yet been identified at the molecular level; however, an insertion/deletion polymorphism is p resent 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 tha t the ACE gene polymorphism could affect the predisposition to myocard ial 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 cell s, 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 t he ECTIM study (n=1086). Plasma ACE level did not differ between patie nts and control subjects in the older age group (greater than or equal to 55 years) but was higher in patients than in control subjects in t he younger age group (<55 years); P<.005 after adjustment on ACE IID a nd other risk factors. In patients, plasma ACE levels decreased with a ge (R=-.225, P<10(-4)), but in control subjects no such trend was obse rved. In the low-risk group (ApoB <1.25 mg/dL, body mass index <26 kg/ m(2), and not treated with hypolipidemic drugs), plasma ACE level was increased in patients when compared with control subjects among homozy gotes and heterozygotes for the ACE I allele (P<.015). Analysis of the distribution of plasma ACE by using commingling analysis conditional on the marker genotype ACE IID enabled us to infer the frequencies and effects of the postulated ACE Ss genotypes. The results suggest that the higher plasma ACE levels in patients than in control subjects in t he younger age group were due to a difference in frequency of the post ulated S allele (.47 versus .36).Conclusions These results extend our previous findings and indicate that plasma ACE level may be a risk fac tor for MI, independent of the ACE I/D polymorphism.