title: Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability.
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.
  
  
  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.
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Hilla-Lee
authors.initials: HL
authors.lastname: Veiner
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Rostic
authors.initials: R
authors.lastname: Gorbatov
authors.affiliation: Harvard Clinical Research Institute, Boston, MA, USA; Boston University School of Public Health, Boston, MA, USA.
authors.forename: Moshe
authors.initials: M
authors.lastname: Vardi
authors.affiliation: Harvard Clinical Research Institute, Boston, MA, USA; Boston University School of Public Health, Boston, MA, USA.
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Doros
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Miller-Lotan
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Zohar
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Rabea
authors.initials: R
authors.lastname: Asleh
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Nina S
authors.initials: NS
authors.lastname: Levy
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Levi J
authors.initials: LJ
authors.lastname: Goldfarb
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel; University of Toronto Faculty of Medicine, Toronto, Canada.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Berk
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Haas
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Shalom
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Edith
authors.initials: E
authors.lastname: Suss-Toby
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Kam
authors.affiliation: Rambam Medical Center, Haifa, Israel.
authors.forename: Marielle
authors.initials: M
authors.lastname: Kaplan
authors.affiliation: Rambam Medical Center, Haifa, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Tamir
authors.affiliation: Rambam Medical Center, Haifa, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Ziskind
authors.affiliation: Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel. Electronic address: alevy@tx.technion.ac.il.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Levy
mesh_terms: D000483:Alleles; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D016122:Brachiocephalic Trunk / Q000473:pathology; D019587:Dietary Supplements; D018450:Disease Progression; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010100:Oxygen / Q000737:chemistry; D058226:Plaque, Atherosclerotic / Q000235:genetics*; D014810:Vitamin E / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D006242:Haptoglobins; D014810:Vitamin E; D010100:Oxygen
keywords: Brachiocephalic artery plaque; Diabetes; Haptoglobin; Pharmacogenomics; Vitamin E