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(Stroke. 2006;37:2917.)
© 2006 American Heart Association, Inc.

Original Contributions

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 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.

Correspondence to Mahmoud Zureik, MD, PhD, INSERM U744, Institut Pasteur de Lille, 1 rue Calmette, BP 245-59019 LILLE cedex, France. 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, 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 4 homozygotes (adjusted odds ratio=2.12, 95% CI=1.27 to 3.53) and less frequent in 2 carriers (adjusted odds ratio=0.79, 95% CI=0.66 to 0.95) compared with 3 homozygotes. Adjusting for and stratifying on lipid levels did not modify these results. CCA-IMT was higher in carriers of the 34 genotype (mean CCA-IMT=0.744 mm versus 0.732 mm for the 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 .

Conclusions— This study, conducted on a large population cohort of French elderly, demonstrated that carotid plaques were significantly associated with the apoE 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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