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on November 9, 2006

Stroke. 2006
Published online before print November 9, 2006, doi: 10.1161/01.STR.0000249011.94055.00
A more recent version of this article appeared on December 1, 2006
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Submitted on August 2, 2006
Accepted on August 14, 2006

New Insight Into the Association of Apolipoprotein E Genetic Variants With Carotid Plaques and Intima-Media Thickness

Stéphanie Debette MD; Jean-Charles Lambert PhD; Jérôme Gariépy MD; Nathalie Fievet MSc; Christophe Tzourio MD, PhD; Jean-Françoise Dartigues MD; Karen Ritchie MD, PhD; Anne-Mary Dupuy MSc; Annick Alpérovitch MD; Pierre Ducimetière PhD; Philippe Amouyel MD, PhD; and Mahmoud Zureik MD, PhD*

From the Department of Neurology, University Hospital of Lille (S.D.), Lille, France; and INSERM Units 744 (M.Z., P.A., N.F., J.C.L.), 780 (P.D.), 593 (J.F.D.), 708 (C.T., A.A.), and E 0361 (K.R., A.M.D.), Center for Cardiovascular Preventive Medicine, Hôpital Broussais (J.G.), Paris, France.

* To whom correspondence should be addressed. E-mail: mahmoud.zureik{at}pasteur-lille.fr.

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, {varepsilon} 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 {varepsilon}4 homozygotes (adjusted odds ratio=2.12, 95% CI=1.27 to 3.53) and less frequent in {varepsilon}2 carriers (adjusted odds ratio=0.79, 95% CI=0.66 to 0.95) compared with {varepsilon}3 homozygotes. Adjusting for and stratifying on lipid levels did not modify these results. CCA-IMT was higher in carriers of the {varepsilon}34 genotype (mean CCA-IMT=0.744 mm versus 0.732 mm for the {varepsilon}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 {varepsilon}.

Conclusions--This study, conducted on a large population cohort of French elderly, demonstrated that carotid plaques were significantly associated with the apoE {varepsilon} polymorphism independently of the -219 polymorphism and vascular risk factors, in particular lipid levels.


Key words: apolipoproteins • carotid arteries • epidemiology • genetics • plaque




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