Vitamin E therapy results in a reduction in HDL function in individuals with diabetes and the haptoglobin 2-1 genotype
Dan Farbstein, Shany Blum, Mordechai Pollak, Roy Asaf, Hilla Lee Viener, Orit Lache, Rabea Asleh, Rachel Miller-Lotan, Ido Barkay, Michael Star, Avery Schwartz, Shiri Kalet-Littman, David Ozeri, Jacob Vaya, Hagai Tavori, Moshe Vardi, Arie Laor, Stephen E Bucher, Yefim Anbinder, Doron Moskovich, Nur Abbas, Netta Perry, Yishai Levy, Andrew P Levy, Dan Farbstein, Shany Blum, Mordechai Pollak, Roy Asaf, Hilla Lee Viener, Orit Lache, Rabea Asleh, Rachel Miller-Lotan, Ido Barkay, Michael Star, Avery Schwartz, Shiri Kalet-Littman, David Ozeri, Jacob Vaya, Hagai Tavori, Moshe Vardi, Arie Laor, Stephen E Bucher, Yefim Anbinder, Doron Moskovich, Nur Abbas, Netta Perry, Yishai Levy, Andrew P Levy
Abstract
Objective: Vitamin E provides cardiovascular protection to individuals with diabetes and the haptoglobin 2-2 genotype but appears to increase cardiovascular risk in individuals with diabetes and the haptoglobin 2-1 genotype. We have previously demonstrated that the haptoglobin protein is associated with HDL and that HDL function and its oxidative modification are haptoglobin genotype dependent. We set out to test the hypothesis that the pharmacogenetic interaction between the haptoglobin genotype on cardiovascular risk might be secondary to a parallel interaction between the haptoglobin genotype and vitamin E on HDL function.
Research design and methods: Fifty-nine individuals with diabetes and the haptoglobin 2-1 or 2-2 genotypes were studied in a double-blind placebo controlled crossover design. Participants were treated with either vitamin E (400IU) or placebo for 3 months and crossed over for an equivalent duration. Serum was collected at baseline and after the completion of each treatment. HDL functionality as well as HDL associated markers of oxidation and inflammation were measured after each interval in HDL purified from the cohort.
Results: Compared to placebo, vitamin E significantly increased HDL function in haptoglobin 2-2 but significantly decreased HDL function in haptoglobin 2-1. This pharmacogenetic interaction was paralleled by similar non-significant trends in HDL associated lipid peroxides, glutathione peroxidase, and inflammatory cargo.
Conclusion: There exists a pharmacogenetic interaction between the haptoglobin genotype and vitamin E on HDL function (clinicaltrials.gov NCT01113671).
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Source: PubMed