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American Journal of Epidemiology Advance Access published online on June 7, 2006
American Journal of Epidemiology, doi:10.1093/aje/kwj202
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.
Received December 5, 2005
Accepted February 17, 2006

ORIGINAL CONTRIBUTIONS

Apolipoprotein E Polymorphisms Predict Low Density Lipoprotein Cholesterol Levels and Carotid Artery Wall Thickness but Not Incident Coronary Heart Disease in 12,491 ARIC Study Participants

Kelly A. Volcik 1, Ruth Ann Barkley 1, Richard G. Hutchinson 2, Thomas H. Mosley 2, Gerardo Heiss 3, A. Richey Sharrett 4, Christie M. Ballantyne 5, and Eric Boerwinkle 1 *

1 Human Genetics Center, University of Texas Health Science Center, Houston, TX
2 Department of Medicine, University of Mississippi Medical Center, Jackson, MS
3 Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, NC
4 Department of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, MD
5 Department of Medicine, Baylor College of Medicine, Houston, TX

* To whom correspondence should be addressed.
Eric Boerwinkle, E-mail: eric.boerwinkle{at}uth.tmc.edu


  Abstract

Elevated levels of low density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease, and recent advancements have provided evidence that carotid artery intima-media thickness (IMT) is associated with increased occurrence of cardiovascular events. Apolipoprotein E (ApoE) has been widely studied in regard to its role in lipid transport and metabolism, but the role that ApoE genetic variation plays in relation to carotid artery IMT and risk of incident coronary heart disease remains a subject of debate. In 1987-2001, the authors examined the effect of each ApoE allele ({varepsilon}2, {varepsilon}3, {varepsilon}4) on LDL cholesterol and carotid IMT, as well as the association with coronary heart disease risk, in 12,491 participants of the US Atherosclerosis Risk in Communities Study. ApoE {varepsilon}2, {varepsilon}3, and {varepsilon}4 allele frequencies were determined, respectively, in Whites (0.08, 0.77, 0.15) and African Americans (0.11, 0.67, 0.22). These alleles did not predict incident coronary heart disease in either racial group. The ApoE {varepsilon}2 allele was associated with lower LDL cholesterol and the {varepsilon}4 allele with higher LDL cholesterol in both Whites and African Americans. The ApoE {varepsilon}2 and {varepsilon}4 alleles were associated with carotid IMT measures in both racial groups, but, after adjusting for lipid parameters, only the {varepsilon}4 allele was associated with carotid IMT measures in African Americans.

Keywords: apolipoproteins E; carotid arteries; coronary disease; lipoproteins, LDL cholesterol; polymorphism, genetic.
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