Genetic variation in the
apolipoprotein E (
APOE) gene is a significant determinant of variation in plasma
cholesterol levels and it also affects the risk of
coronary artery disease (CAD). We examined the association of the
APOE polymorphism with CAD severity in women from the NHLBI-sponsored Women's
Ischemia Syndrome Evaluation (WISE) study. Quantitative coronary angiography was used to classify subjects as having normal/minimal CAD (<20%
stenosis), mild CAD (20-49%
stenosis) and significant CAD (>or=50%
stenosis). The women with or=50%
stenosis were further stratified according to the number of vessel disease they have (one, two, or three). In white subjects, the frequency of
APOE*4 carriers (3/4 and 4/4 genotypes) was significantly higher in the combined mild/significant CAD group (>or=20%
stenosis) compared with the normal/minimal CAD group (<20%
stenosis) (31.3 vs. 19.2%; P=0.025) with an adjusted OR of 2.40 (95% CI: 1.47-3.93; P=0.0005). Furthermore, the
APOE*4 allele was found to be significantly associated with the increased vessel disease number (chi(2)=8.04; P=0.0046). This association of the
APOE*4 allele with CAD severity was present only in women with family history of CAD.
APOE polymorphism also showed significant associations with increasing plasma total
cholesterol (P=0.01) and
low-density lipoprotein (
LDL)-cholesterol (P<0.001) in whites. These data support the hypothesis that the
APOE*4 allele is an independent risk factor not only for the presence of CAD and
hyperlipidemia, but also for the angiographic severity of CAD in white women with a family history of disease.