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Journal of Lipid Research, Vol. 45, 1868-1875, October 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Association of APOE genotype with carotid atherosclerosis in men and women

Roberto Elosua^*,, Jose M. Ordovas, L. Adrienne Cupples^*,, Caroline S. Fox^,**,, Joseph F. Polak, Philip A. Wolf^,***, Ralph A. D'Agostino, Sr. and Christopher J. O'Donnell^1,,,

National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA
Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Departments of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
^** Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
^*** Departments of Neurology and Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA
^* Department of Biostatistics, Boston University, Boston, MA
United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD

¹ To whom correspondence should be addressed. e-mail: codonnell{at}partners.org

The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30–0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm).

The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men.

Supplementary key words genetics • atherosclerosis • carotid artery • lipoprotein • apolipoprotein E genotype

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