Submitted on October 11, 2005
Revised on January 27, 2006
Accepted on February 10, 2006
Variability at the APOA5 locus is associated with carotid atherosclerosis with a modifying effect of obesity: the Framingham Heart Study
Roberto Elosua, Jose M. Ordovas, L. Adrienne Cupples, Chao-Qiang Lai, Serkalem Demissie, Caroline S. Fox, Joseph F. Polak, Philip A. Wolf, Ralph A. D’Agostino, and Christopher J. O'Donnell
National Heart, Lung adn Blood Institute's Framingham Heart Study, Framingham, MA 01702
Corresponding Author: codonnell{at}nih.gov
Objective: Genetic variation at the apolipoprotein A5 (APOA5) locus is associated with elevated 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. Methods and results: 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 were 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 to the wild-type haplotype (0.75 mm 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. Conclusions: APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity is independent of fasting triglyceride levels.
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