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Curr Diab Rep. 2017 Jun;17(6):42. doi: 10.1007/s11892-017-0868-1.

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

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Institute of Endocrinology, Diabetes and Metabolism, Rambam HealthCare Campus, Haifa, Israel.
Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
Clalit Health Services, Haifa and western Galilee District, Haifa, Israel.



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.


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.


Cardiovascular disease; Haptoglobin; High-density lipoproteins; Oxidative stress; Vitamin E

[Indexed for MEDLINE]

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