Background The insertion/deletion polymorphism of the
angiotensin-converting enzyme (ACE) and the A1166C polymorphism of the
angiotensin-II AT1 receptor (AT1R) have been extensively investigated as
possible risk factors for myocardial infarction (MI).
Design and methods Genetic association, case-control study, specifically
designed to investigate the association of the above-mentioned
polymorphisms with risk of MI in a homogeneous, low coronary risk,
Caucasian population. The study population consisted of 1603 consecutive
patients with acute MI who were recruited from nine clinics, located in
three cities, and 699 unrelated adults who were randomly selected from
the city catalogues.
Results In univariate analysis, the DD genotype was found to be more
prevalent among controls (40.8 vs. 35.2%, P=0.011). In multivariate
analysis adjusted for age, gender, smoking status, diabetes mellitus,
hypercholesterolaemia, hypertension and family history of coronary
artery disease, the presence of the DD genotype was independently and
negatively associated with risk of AMI (RR = 0.743,95% CI =
0.595-0.927, P= 0.008). The CC genotype was not found to be
significantly associated with risk of M I, either in univariate (6.2 vs.
6.4%, P=0.856), or in multivariate analysis adjusted for the same
confounders (RR = 0.743, 95% Cl = 0.473-1.167, P= 0.197).
Conclusions Contrary to previous reports, in this study the DD genotype
of the ACE gene, but not the CC genotype of the AT1R gene, was
associated with a lower risk of MI. Our results emphasize the complexity
of genotype-phenotype interactions in the pathogenesis of ischaemic
heart disease and question the previously hypothesized role of the DD
genotype on risk of acute myocardial infarction. (C) 2004 The European
Society of Cardiology