Interaction Between the Haptoglobin Genotype and Vitamin E on Cardiovascular Disease in Diabetes

  • Irit HochbergEmail author
  • Elliot M. Berinstein
  • Uzi Milman
  • Chen Shapira
  • Andrew P. Levy
Lifestyle Management to Reduce Diabetes/Cardiovascular Risk (B Conway and H Keenan, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Lifestyle Management to Reduce Diabetes/Cardiovascular Risk


Purpose of Review

Despite compelling evidence regarding the importance of oxidant stress in the development of vascular complications and observational studies suggesting that vitamin E may be protective from these complications, multiple clinical trials have failed to show benefit from vitamin E supplementation in the prevention of vascular complications in diabetes. One possible explanation for this failure of vitamin E may have been inappropriate patient selection. This review seeks to provide the clinical evidence and mechanistic basis for why a subset of individuals defined by their haptoglobin (Hp) genotype may derive cardiovascular protection by vitamin E supplementation.

Recent Findings

Clinical trial data from the HOPE, ICARE, and WHS studies is presented showing a pharmacogenomic interaction between the Hp genotype and vitamin E on the development of CVD. Specifically, in individuals with diabetes and the Hp2-2 genotype, vitamin E has been shown to be associated with an approximately 35% reduction in CVD. Cardioprotection by vitamin E in individuals with the Hp2-2 genotype appears to be mediated in part by an improvement in HDL functionality as demonstrated in three independent trials in both type 1 diabetes and type 2 diabetes.


Vitamin E may provide benefit in reducing CVD in Hp2-2 individuals with diabetes. However, in order for this pharmacogenomic algorithm to be accepted as a standard of care and used clinically, an additional large prospective study will need to be performed.


Vitamin E Haptoglobin Cardiovascular disease High-density lipoproteins Oxidative stress 


Compliance with Ethical Standards

Conflict of Interest

Irit Hochberg, Elliot M. Berinstein, Uzi Milman, and Chen Shapira declare that they have no conflict of interest.

Andrew P. Levy reports that his institution is the owner of a patent which claims to use haptoglobin genotyping to predict the risk of developing cardiovascular disease in diabetes and the use of vitamin E to reduce this risk; and it is licensed to In Vitro (patent is owned by BioRap Technologies of the Technion Israel Institute of Technology).

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in any of the studies reviewed in this article. This article does not contain any studies with animals performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Irit Hochberg
    • 1
    Email author
  • Elliot M. Berinstein
    • 2
  • Uzi Milman
    • 2
    • 3
  • Chen Shapira
    • 2
    • 3
  • Andrew P. Levy
    • 2
  1. 1.Institute of Endocrinology, Diabetes and MetabolismRambam HealthCare CampusHaifaIsrael
  2. 2.Technion Faculty of MedicineTechnion Israel Institute of TechnologyHaifaIsrael
  3. 3.Clalit Health ServicesHaifaIsrael

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