The relationship between risk factor levels and presence of coronary artery calcification is dependent on Apolipoprotein E genotype

An important research question in the study of the genetics of coronary artery disease (CAD) is whether information about genetic variation will improve our ability to predict CAD beyond established risk factors. This question is especially relevant to the goal of identifying young, asymptomatic adults with coronary atherosclerosis who would benefit most from interventions to reduce risk. Coronary artery calcification (CAC) detected by electron-beam computed tomography is a relatively new method for detecting coronary atherosclerosis in asymptomatic individuals that has been shown to be a more accurate indicator of coronary atherosclerosis in asymptomatic individuals than other noninvasive techniques. In a study of asymptomatic women (n = 169) and men (n = 160) between the ages of 20 and 59 representative of the Rochester, Minnesota population, we used logistic regression to ask whether the most common Apolipoprotein (Apo) E genotypes (epsilon 3/2, epsilon 3/3, and epsilon 4/3) predict the presence of CAC, The addition of information about ApoE genotypes to logistic models containing each separate risk factor did not improve prediction of CAC (P > 0.10 in both women and men). However, there was significant evidence (P < 0.10) that associations between variation in the probability of having CAC and variation in body mass index, plasma total cholesterol, and plasma ApoB in men and body mass index, plasma triglycerides, plasma ApoA1, and plasma ApoE in women were dependent on ApoE genotype. Thus, variation in the gene coding for ApoE may play a role in determining the contribution of established risk factors to risk of CAC.