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The polymorphism of the apolipoprotein E gene (∊2, ∊3, ∊4) 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 (2/∊2, ∊2/∊3), E3 (∊3/∊3), and E4 (∊4/∊4, ∊3/∊4).Apolipoprotein E allele frequencies were ∊2 = 0.08, ∊3 = 0.79, ∊4 = 0.13. Subjects with ∊4 allele had the highest levels of total serum cholesterol and low density lipoprotein cholesterol; subjects with ∊2 allele had the lowest levels (P < 0.001). Considering carotid hypertrophy as intima–media thickness > 660 μm, and radial hypertrophy as intima–media thickness > 260 μm, 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 ∊2 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 ∊2 allele is related to wall hypertrophy in carotid artery despite favourable effect on the lipid profile.