Association between the apolipoprotein E polymorphism and arterial wall thickness in asymptomatic adults.

Abstract

The polymorphism of the apolipoprotein E gene (epsilon2, epsilon3, epsilon4) affects plasma cholesterol but the relationship with artery wall thickness has indicated contradictory results. This study investigated the relationship between apolipoprotein E polymorphism and vascular phenotypes of the carotid and radial arteries, two arterial sites differently affected by atherosclerosis. We studied a cohort of 320 Caucasian subjects (age 49 +/- 12 years) without evidence of cardiovascular disease. Structural (internal diameter and wall thickness) and functional phenotypes (compliance, distensibility) were evaluated for the common carotid and the radial arteries using high resolution echo-tracking devices. Genotypes of apolipoprotein E were determined by allele-specific oligonucleotides hybridization. Because of the relative low frequency of some apolipoprotein E genotypes, they were designated as E2 (epsilon2/epsilon2, epsilon2/epsilon3), E3 (epsilon3/epsilon3), and E4 (epsilon4/epsilon4, epsilon3/epsilon4). Apolipoprotein E allele frequencies were epsilon2 = 0.08, epsilon3 = 0.79, epsilon4 = 0.13. Subjects with epsilon4 allele had the highest levels of total serum cholesterol and low density lipoprotein cholesterol; subjects with epsilon2 allele had the lowest levels (P < 0.001). Considering carotid hypertrophy as intima-media thickness > 660 microm, and radial hypertrophy as intima-media thickness > 260 microm, a logistic regression model testing determinants of arterial hypertrophy (age, gender, weight, systolic blood pressure, smoking habits, and total serum cholesterol) observed a significant and positive association between carotid hypertrophy and epsilon2 allele carriers (P= 0.03). In contrast, no association was found between hypertrophy and apolipoprotein E genotypes for the radial artery. No association was observed between the apolipoprotein E genotypes and functional artery parameters. In subjects without any evidence of cardiovascular disease, the presence of the epsilon2 allele is related to wall hypertrophy in carotid artery despite favourable effect on the lipid profile.