Apolipoprotein E Gene Polymorphisms Are Associated With Carotid Plaque Formation but Not With Intima-Media Wall Thickening

Abstract

Background and Purpose— Several studies have investigated the role of apolipoprotein E (apoE) polymorphisms on carotid intima-media thickness (IMT) with conflicting results. The objective of this study was to use a large, community-based population to investigate associations between apoE gene polymorphisms and cardiovascular disease–associated phenotypes: IMT, carotid artery plaque, and low- (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Methods— ApoE genotypes were determined in 1109 randomly selected community subjects with an equal man-to-woman ratio and equal numbers in each age decile who were 27 to 77 years of age and had bilateral carotid B-mode ultrasound and cardiovascular risk factor measurements. Results— Multivariate analyses, stratified by sex, demonstrated an association between apoE genotypes and LDL-C levels in men ( P =0.03) and women ( P <0.001). A significant linear trend in increasing LDL-C (β=0.33 per unit change in genotype; SE=0.07; P <0.001) levels with increasing number of ε4 alleles across the ε3/ε3, ε3/ε4, or ε4/ε4 genotypes was observed in women but not in men. The associations were independent of age, diastolic blood pressure, and history of diabetes mellitus. Multivariate analyses found a log-additive trend in risk of developing carotid plaque with increasing numbers of ε4 alleles across the ε3/ε3, ε3/ε4, and ε4/ε4 genotypes (odds ratio [OR], 1.72 per unit change in genotype; 95% CI, 1.05 to 2.80; P =0.03) in men. There was no association between plaque frequency and the ε4 allele in women. However, the ε2/ε3 genotype was shown to be associated with a lower OR (OR, 0.40; 95% CI, 0.17 to 0.91; P =0.03) for carotid plaques relative to the ε3/ε3 genotype in women. The associations were independent of age and standard vascular risk factors. There were no significant independent associations between apoE genotypes and IMT in either men or women. Conclusions— Our data suggest that polymorphisms in the apoE gene are significantly associated with LDL-C levels and increased risk of carotid plaque formation in men but not IMT in either men or women.