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Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Ireland NLM ID: 0242543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1484 (Electronic) Linking ISSN: 00219150 NLM ISO Abbreviation: Atherosclerosis Subsets: MEDLINE
    • Publication Information:
      Publication: Limerick : Elsevier
      Original Publication: Amsterdam, Elsevier.
    • Subject Terms:
    • 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.
      (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
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    • Grant Information:
      R01 DK085226 United States DK NIDDK NIH HHS; R01DK085226 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Keywords: Brachiocephalic artery plaque; Diabetes; Haptoglobin; Pharmacogenomics; Vitamin E
    • Accession Number:
      0 (Antioxidants)
      0 (Apolipoproteins E)
      0 (Haptoglobins)
      1406-18-4 (Vitamin E)
      S88TT14065 (Oxygen)
    • Publication Date:
      Date Created: 20150126 Date Completed: 20160331 Latest Revision: 20181113
    • Publication Date:
      20220902
    • Accession Number:
      PMC4331216
    • Accession Number:
      10.1016/j.atherosclerosis.2015.01.008
    • Accession Number:
      25618031