J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M500446-JLR200 on February 11, 2006

Papers In Press, published online ahead of print May 1, 2006
J. Lipid Res., doi:10.1194/jlr.M500446-JLR200
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Journal of Lipid Research, Vol. 47, 990-996, May 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Studyboxs

Roberto Elosua*,{dagger},§, Jose M. Ordovas*, L. Adrienne Cupples{dagger},**, Chao-Qiang Lai*, Serkalem Demissie{dagger}, Caroline S. Fox**,{dagger}{dagger},§§, Joseph F. Polak***, Philip A. Wolf**,{dagger}{dagger}{dagger}, Ralph B. D'Agostino, Sr.** and Christopher J. O'Donnell1,**,§§,§§§

* U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA
{dagger} Department of Biostatistics, Boston University School of Public Health, Boston, MA
§ Institut Municipal d'Investigació Mèdica, Barcelona, Spain
** National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA
{dagger}{dagger} Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
§§ National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
*** Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
{dagger}{dagger}{dagger} Departments of Neurology and Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA
§§§ Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA

boxs The online version of this article (available at http://www.jlr.org) contains an additional two figures.

Published, JLR Papers in Press, February 11, 2006.

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

Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (–1131T>C, –3A>G, 56C>G, IVS3+476G >A, and 1259T>C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C>G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the –1131T >C, –3A>G, IVS3+476G>A, and 1259T>C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels.

Supplementary key words apolipoproteins • carotid arteries • epidemiology • genetics • apolipoprotein A5 gene


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