New insight into the association of apolipoprotein E genetic variants with carotid plaques and intima-media thickness

Background and Purpose - Carotid plaques and elevated carotid artery intima-media thickness (IMT) are major predictors of vascular morbidity and mortality. Our aim was to test their association with 2 polymorphisms of the apolipoprotein E (apoE) gene, epsilon and - 219G/T. Methods - The study was performed on 5856 subjects aged >= 65 years recruited from the French population for the Three-City Study. Carotid ultrasound examination included an assessment of atherosclerotic plaques in the extracranial carotid arteries and a measurement of IMT in the common carotid arteries (CCA) at a site free of plaques. The genetic association was tested using genotype and haplotype analyses. Results - In a multivariate analysis including both polymorphisms and vascular risk factors, carotid plaques were more frequent in epsilon 4 homozygotes (adjusted odds ratio = 2.12, 95% CI = 1.27 to 3.53) and less frequent in epsilon 2 carriers (adjusted odds ratio = 0.79, 95% CI = 0.66 to 0.95) compared with epsilon 3 homozygotes. Adjusting for and stratifying on lipid levels did not modify these results. CCA-IMT was higher in carriers of the epsilon 34 genotype (mean CCA-IMT = 0.744 mm versus 0.732 mm for the epsilon 33 genotype, P = 0.002), but the association disappeared after excluding subjects with carotid plaques. No association was found between the -219 polymorphism and either carotid plaques or CCA-IMT, and there was no interaction or cis-effect between -219 and epsilon. Conclusions - This study, conducted on a large population cohort of French elderly, demonstrated that carotid plaques were significantly associated with the apoE epsilon polymorphism independently of the -219 polymorphism and vascular risk factors, in particular lipid levels.