Genotype Distribution of Angiotensin-Converting Enzyme Polymorphism in Australian Healthy and Coronary Populations and Relevance to Myocardial Infarction and Coronary Artery Disease

Abstract

Angiotensin-converting enzyme is a key component of the renin-angiotensin system that plays an important role in cardiovascular regulation. An association between the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism and increased coronary risk has been found in some studies but not in others. To explore this further in an Australian 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 children aged 6 to 13 years. We also explored associations in the patients between the angiotensin-converting enzyme I/D polymorphism and a history of myocardial infarction and coronary artery disease severity assessed by the number of major coronary arteries with more than 50% luminal obstructions and by the Green Lane coronary score. The frequencies 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 significantly different (chi 2 = 23.69, P < .0001) from that in the school children, in whom the genotype distribution was in Hardy-Weinberg equilibrium (I/I, 0.21; I/D, 0.54; D/D, 0.25). There was also a significant 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 angiotensin-converting enzyme polymorphism and the number of significantly stenosed coronary arteries (chi 2 = 2.069, P = .91). We conclude that the D/D genotype is a significant predictor for coronary artery disease events in the Australian white population but is not a marker for angiographically assessed coronary artery disease severity. The angiotensin-converting enzyme genotype-associated increased risk for coronary events may be mediated more by angiotensin II-induced coronary vasoconstriction than by an increase in injury-related smooth muscle cell proliferation in the coronary vasculature.

Angiotensin I-converting enzyme gene polymorphism, coronary artery disease and myocardial infarction. An angiographically controlled study

“…A recent study in patients undergoing coronary angiography implied that ACE insertion/deletion polymorphism is not associated with coronary lesions themselves, but with the occurrence of myocardial infarction in patients with coronary heart disease [11] . Similar results were obtained in an Australian population, in whom there was a strong association of the ACE DD genotype with the presence of coronary artery disease or a history of myocardial infarction, but not with the severity of coronary artery disease, in comparison to a cohort of healthy school children [12] .…”

Angiotensin-converting enzyme gene polymorphism and premature coronary heart disease

“…Despite our negative result and the recent conclusion, from the large ISIS study and meta-analysis of the larger earlier studies, that ACE genotype plays little, if any, role in MI [3], the greater frequency of the D allele or the DD genotype reported in children with parents [15] or grandparents [16] with a history of MI or CHD strengthens the concept that there is a real relationship between these factors in some populations. If so, the commonly studied D\I polymorphism may not itself be responsible, but instead one or more of the many polymorphisms in the ACE gene that have been described recently [17].…”

Angiotensin-Converting Enzyme I/D Polymorphism in Behçet’s Disease

“…The absence of this fragment (deletion or D allele) is associated with relatively higher ACE activity [8] . The allelic frequency of the ACE gene varies among different racial and ethnic groups [9,10] .…”