New insight into the association of apolipoprotein E genetic variants with carotid plaques and intima-media thickness.
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.
Debette
Stéphanie
S
Department of Neurology, University Hospital of Lille, Lille, France.
Lambert
Jean-Charles
JC
Gariépy
Jérôme
J
Fievet
Nathalie
N
Tzourio
Christophe
C
Dartigues
Jean-Françoise
JF
Ritchie
Karen
K
Dupuy
Anne-Mary
AM
Alpérovitch
Annick
A
Ducimetière
Pierre
P
Amouyel
Philippe
P
Zureik
Mahmoud
M
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*
D001057:Apolipoproteins E