Journal
ATHEROSCLEROSIS
Volume 239, Issue 1, Pages 232-239Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2015.01.008
Keywords
Diabetes; Haptoglobin; Vitamin E; Pharmacogenomics; Brachiocephalic artery plaque
Funding
- NIH [RO1DK085226]
- Israel Science Foundation
- Rappaport Family Medical Research Institute
- Frances Brody Chair in Life Sciences at the Technion
- U Toronto
- Technion
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Objective: Homozygosity for a 1.7 kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2-3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. Methods and Results: Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE(-/-) background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. Conclusions: These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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