1. Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability
- Author
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Yaniv Zohar, Rostic Gorbatov, Gheorghe Doros, Nina S. Levy, Rabea Asleh, Edmond Sabo, Thomas A. Berk, Tali Haas, Rachel Miller-Lotan, Levi J. Goldfarb, Andrew P. Levy, Adi Kam, Hilla-Lee Viener, Moshe Y. Vardi, Anna Ziskind, Marielle Kaplan, Ronit Tamir, Hadar Shalom, and Edith Suss-Toby
- Subjects
Apolipoprotein E ,medicine.medical_specialty ,Genotype ,medicine.medical_treatment ,Population ,Mice, Transgenic ,Antioxidants ,Article ,Apolipoproteins E ,Mice ,Polymorphism (computer science) ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Vitamin E ,education ,Alleles ,Brachiocephalic Trunk ,education.field_of_study ,biology ,Haptoglobins ,Haptoglobin ,Homozygote ,medicine.disease ,Plaque, Atherosclerotic ,Mice, Inbred C57BL ,Oxygen ,Endocrinology ,Immunology ,Dietary Supplements ,biology.protein ,Disease Progression ,Cardiology and Cardiovascular Medicine - Abstract
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.
- Published
- 2014