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.
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 1-1mice 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.
Authors: Andrew P Levy; Joanne E Levy; Shiri Kalet-Litman; Rachel Miller-Lotan; Nina S Levy; Roy Asaf; Julia Guetta; Chingwen Yang; K Raman Purushothaman; Valentin Fuster; Pedro R Moreno Journal: Arterioscler Thromb Vasc Biol Date: 2006-10-26 Impact factor: 8.311
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Authors: Renu Virmani; Frank D Kolodgie; Allen P Burke; Aloke V Finn; Herman K Gold; Thomas N Tulenko; Steven P Wrenn; Jagat Narula Journal: Arterioscler Thromb Vasc Biol Date: 2005-07-21 Impact factor: 8.311
Authors: Leah E Cahill; Andrew P Levy; Stephanie E Chiuve; Majken K Jensen; Hong Wang; Nawar M Shara; Shany Blum; Barbara V Howard; Jennifer K Pai; Kenneth J Mukamal; Kathryn M Rexrode; Eric B Rimm Journal: J Am Coll Cardiol Date: 2013-01-09 Impact factor: 24.094
Authors: Jeremy N Adams; Amanda J Cox; Barry I Freedman; Carl D Langefeld; J Jeffrey Carr; Donald W Bowden Journal: Cardiovasc Diabetol Date: 2013-02-11 Impact factor: 9.951