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 MoskovichNur Abbas, Netta Perry, Yishai Levy, Andrew P. Levy

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 (400. IU) 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).

Original languageEnglish (US)
Pages (from-to)240-244
Number of pages5
JournalAtherosclerosis
Volume219
Issue number1
DOIs
StatePublished - Nov 2011
Externally publishedYes

Fingerprint

Haptoglobins
Vitamin E
Genotype
Pharmacogenetics
Placebos
Distance Counseling
Lipid Peroxides
Glutathione Peroxidase
Cross-Over Studies
Research Design
Inflammation

Keywords

  • Cholesterol efflux
  • Diabetes
  • Haptoglobin
  • HDL
  • Oxidation
  • Tocopherol
  • Vitamin E

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Vitamin E therapy results in a reduction in HDL function in individuals with diabetes and the haptoglobin 2-1 genotype. / Farbstein, Dan; Blum, Shany; Pollak, Mordechai; Asaf, Roy; Viener, Hilla Lee; Lache, Orit; Asleh, Rabea; Miller-Lotan, Rachel; Barkay, Ido; Star, Michael; Schwartz, Avery; Kalet-Littman, Shiri; Ozeri, David; Vaya, Jacob; Tavori, Hagai; Vardi, Moshe; Laor, Arie; Bucher, Stephen E.; Anbinder, Yefim; Moskovich, Doron; Abbas, Nur; Perry, Netta; Levy, Yishai; Levy, Andrew P.

In: Atherosclerosis, Vol. 219, No. 1, 11.2011, p. 240-244.

Research output: Contribution to journalArticle

Farbstein, D, Blum, S, Pollak, M, Asaf, R, Viener, HL, Lache, O, Asleh, R, Miller-Lotan, R, Barkay, I, Star, M, Schwartz, A, Kalet-Littman, S, Ozeri, D, Vaya, J, Tavori, H, Vardi, M, Laor, A, Bucher, SE, Anbinder, Y, Moskovich, D, Abbas, N, Perry, N, Levy, Y & Levy, AP 2011, 'Vitamin E therapy results in a reduction in HDL function in individuals with diabetes and the haptoglobin 2-1 genotype', Atherosclerosis, vol. 219, no. 1, pp. 240-244. https://doi.org/10.1016/j.atherosclerosis.2011.06.005
Farbstein, Dan ; Blum, Shany ; Pollak, Mordechai ; Asaf, Roy ; Viener, Hilla Lee ; Lache, Orit ; Asleh, Rabea ; Miller-Lotan, Rachel ; Barkay, Ido ; Star, Michael ; Schwartz, Avery ; Kalet-Littman, Shiri ; Ozeri, David ; Vaya, Jacob ; Tavori, Hagai ; Vardi, Moshe ; Laor, Arie ; Bucher, Stephen E. ; Anbinder, Yefim ; Moskovich, Doron ; Abbas, Nur ; Perry, Netta ; Levy, Yishai ; Levy, Andrew P. / Vitamin E therapy results in a reduction in HDL function in individuals with diabetes and the haptoglobin 2-1 genotype. In: Atherosclerosis. 2011 ; Vol. 219, No. 1. pp. 240-244.
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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 (400. IU) 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).",
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T1 - Vitamin E therapy results in a reduction in HDL function in individuals with diabetes and the haptoglobin 2-1 genotype

AU - Farbstein, Dan

AU - Blum, Shany

AU - Pollak, Mordechai

AU - Asaf, Roy

AU - Viener, Hilla Lee

AU - Lache, Orit

AU - Asleh, Rabea

AU - Miller-Lotan, Rachel

AU - Barkay, Ido

AU - Star, Michael

AU - Schwartz, Avery

AU - Kalet-Littman, Shiri

AU - Ozeri, David

AU - Vaya, Jacob

AU - Tavori, Hagai

AU - Vardi, Moshe

AU - Laor, Arie

AU - Bucher, Stephen E.

AU - Anbinder, Yefim

AU - Moskovich, Doron

AU - Abbas, Nur

AU - Perry, Netta

AU - Levy, Yishai

AU - Levy, Andrew P.

PY - 2011/11

Y1 - 2011/11

N2 - 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 (400. IU) 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).

AB - 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 (400. IU) 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).

KW - Cholesterol efflux

KW - Diabetes

KW - Haptoglobin

KW - HDL

KW - Oxidation

KW - Tocopherol

KW - Vitamin E

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