Angiotensin-converting enzyme gene polymorphism and carotid wall thickening in a community population

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enz yme (ACE) gene has been associated with an increased risk of coronary heart disease, but whether it is a risk factor for underlying atherosclerosis re mains unclear. Therefore, we examined to see whether the ACE gene deletion polymorphism was associated with carotid wall thickening and atheroscleroti c plaque formation in a large randomly selected community population. A tot al of 1111 subjects, aged 27 to 77 years, with an equal male:female ratio a nd equal numbers in each age decile, were randomly selected from the Perth community population. Mean common carotid intima-medial wall thickness (IMT ) and focal plaque formation were assessed by high-resolution B-mode ultras ound. The ACE gene I/D polymorphism was detected by PCR. The distribution o f the ACE; genotypes conformed to the Hardy-Weinberg equilibrium (DD, 31.0% ; ID, 48.4%; and II, 20.6%). The D allele was strongly correlated in a codo minant fashion with plasma ACE activity (r(s)=0.53, P<0.0001), and accounte d for 33% of the total variance in circulating ACE activity. No significant differences among the ACE genotypes were found with respect to age, sex, a nd conventional risk variables, including a history of hypertension and vas cular disease. The average mean IMT and prevalence of increased IMT and foc al plaque were not significantly different among genotypes in the overall p opulation or in the subset (n=852) who were conventionally low risk by Fram ingham coronary heart disease risk score. Logistic regression analysis sele cted age, systolic blood pressure, pack-years of smoking, LDL cholesterol l evel, waist/hip ratio, and history of hypertension, but not the D allele, a s multivariate predictors of increased IMT and carotid plaque formation. We conclude that, although the ACE I/D polymorphism is strongly related to AC E activity, it is not a risk predictor of carotid wall thickening or focal plaque formation when examined in a large randomly selected community popul ation.