ANGIOTENSIN-CONVERTING ENZYME GENE DELETION ALLELE IS INDEPENDENTLY AND STRONGLY ASSOCIATED WITH CORONARY ATHEROSCLEROSIS AND MYOCARDIAL-INFARCTION

Objective - To investigate the association of the three angiotensin co nverting enzyme (ACE) genotypes, DD, ID, and IF, with the occurrence o r absence of coronary atherosclerosis and with myocardial infarction a nd hypertension. Design - Cohort analysis study. Setting - North-Italy reference centre. Subjects - 388 white Italian patients (281 males; m ean age 60.7 (SD 12.5) years) with proven coronary atherosclerosis (n = 255) or with angiographically normal coronary arteries (n = 133). A further group of 290 healthy blood donors was tested for allele freque ncy comparison. Interventions - ACE/ID polymorphism was analysed with polymerase chain reaction on DNA from white blood cells. Main outcome measures - Coronary atherosclerosis, myocardial infarction, hypertensi on. Results - The D and I allele frequencies were respectively 0.63 an d 0.37 in the overall healthy blood donor group and 0.66 and 0.34 in t he overall study group. In the latter, univariate analysis showed (1) that coronary atherosclerosis (255 patients) was associated with the d eletion allele, with an odds ratio (OR) of 5.78 for DD/II, P < 0.001, and 2.39 for ID/II, P = 0.006; and (2) that myocardial infarction (154 patients) was associated with the DD genotype (OR DD/II = 2.56, P = 0 .007), but not with the ID genotype (OR DD/II 1.96, P = 0.056). Finall y, hypertension proved to be unrelated with the ACE genotype. The dist ribution between the three genotypes of known risk factors for coronar y artery disease was similar. Logistic regression modelling, performed to test the association of the selected risk factors simultaneously w ith coronary atherosclerosis and myocardial infarction, showed that th e deletion allele (whether DD or ID) was the strongest risk factor for atherosclerosis, and that the D allele was significantly associated w ith the risk of infarction (although to a lesser extent than with coro nary atherosclerosis). Conclusion - ACE deletion polymorphism is stron gly and independently associated with coronary atherosclerosis and, to a lesser extent, with myocardial infarction. As such, the results are analogous to what has already been reported in French white, Japanese , and Welsh coronary patients.