title: New insight into the association of apolipoprotein E genetic variants with carotid plaques and intima-media thickness.
abstract: OBJECTIVE
  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 > or =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 epsilon4 homozygotes (adjusted odds ratio=2.12, 95% CI=1.27 to 3.53) and less frequent in epsilon2 carriers (adjusted odds ratio=0.79, 95% CI=0.66 to 0.95) compared with epsilon3 homozygotes. Adjusting for and stratifying on lipid levels did not modify these results. CCA-IMT was higher in carriers of the epsilon34 genotype (mean CCA-IMT=0.744 mm versus 0.732 mm for the epsilon33 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.
authors.affiliation: Department of Neurology, University Hospital of Lille, Lille, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Debette
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gariépy
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fievet
authors.forename: Christophe
authors.initials: C
authors.lastname: Tzourio
authors.forename: Jean-Françoise
authors.initials: JF
authors.lastname: Dartigues
authors.forename: Karen
authors.initials: K
authors.lastname: Ritchie
authors.forename: Anne-Mary
authors.initials: AM
authors.lastname: Dupuy
authors.forename: Annick
authors.initials: A
authors.lastname: Alpérovitch
authors.forename: Pierre
authors.initials: P
authors.lastname: Ducimetière
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Zureik
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D002339:Carotid Arteries / Q000473:pathology; D016893:Carotid Stenosis / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D017539:Tunica Intima / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E