GENOTYPE DISTRIBUTION OF ANGIOTENSIN-CONVERTING ENZYME POLYMORPHISM IN AUSTRALIAN HEALTHY AND CORONARY POPULATIONS AND RELEVANCE TO MYOCARDIAL-INFARCTION AND CORONARY-ARTERY DISEASE

Angiotensin-converting enzyme is a key component of the renin-angioten sin system that plays an important role in cardiovascular regulation. An association between the angiotensin-converting enzyme insertion/del etion (IID) polymorphism and increased coronary risk has been found in some studies but not in others. To explore this further in an Austral ian white population, we compared the ACE genotype distribution in 550 patients aged 37 to 65 years with coronary artery disease documented by angiography with the genotype distribution in 404 healthy school ch ildren aged 6 to 13 years. We also explored associations in the patien ts between the angiotensin-converting enzyme IID polymorphism and a hi story of myocardial infarction and coronary artery disease severity as sessed by the number of major coronary arteries with more than 50% lum inal obstructions and by the Green Lane coronary score. The frequencie s of the angiotensin-converting enzyme genotype in the coronary artery disease patients were 0.236 for I/I, 0.395 for I/D, and 0.369 for D/D genotypes. This distribution with an excess of the D/D genotype was s ignificantly different (chi(2)=23.69, P<.0001) from that in the school children, in whom the genotype distribution was in Hardy-Weinberg equ ilibrium (I/I, 0.21; I/D, 0.54; D/D, 0.25). There was also a significa nt excess of D/D genotype among patients with a history of myocardial infarction (chi(2)=9.42, P=.009), and there was the same D/D excess in the subgroup of children (n=60) with two or more grandparents who had had coronary artery disease. We found no associations between the ang iotensin-converting enzyme polymorphism and the number of significantl y stenosed coronary arteries (chi(2)=2.069, P=.91). We conclude that t he D/D genotype is a significant predictor for coronary artery disease events in the Australian white population but is not a marker for ang iographically assessed coronary artery disease severity. The angiotens in-converting enzyme genotype-associated increased risk for coronary e vents map be mediated more by angiotensin II-induced coronary vasocons triction than by an increase in injury-related smooth muscle cell prol iferation in the coronary vasculature.