title: Vitamin E therapy results in a reduction in HDL function in individuals with diabetes and the haptoglobin 2-1 genotype.
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.
  
  
  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.
  
  
  CONCLUSIONS
  There exists a pharmacogenetic interaction between the haptoglobin genotype and vitamin E on HDL function (clinicaltrials.gov NCT01113671).
authors: Department of Anatomy and Cell Biology, Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors: Dan
authors: D
authors: Farbstein
authors: Shany
authors: S
authors: Blum
authors: Mordechai
authors: M
authors: Pollak
authors: Roy
authors: R
authors: Asaf
authors: Hilla Lee
authors: HL
authors: Viener
authors: Orit
authors: O
authors: Lache
authors: Rabea
authors: R
authors: Asleh
authors: Rachel
authors: R
authors: Miller-Lotan
authors: Ido
authors: I
authors: Barkay
authors: Michael
authors: M
authors: Star
authors: Avery
authors: A
authors: Schwartz
authors: Shiri
authors: S
authors: Kalet-Littman
authors: David
authors: D
authors: Ozeri
authors: Jacob
authors: J
authors: Vaya
authors: Hagai
authors: H
authors: Tavori
authors: Moshe
authors: M
authors: Vardi
authors: Arie
authors: A
authors: Laor
authors: Stephen E
authors: SE
authors: Bucher
authors: Yefim
authors: Y
authors: Anbinder
authors: Doron
authors: D
authors: Moskovich
authors: Nur
authors: N
authors: Abbas
authors: Netta
authors: N
authors: Perry
authors: Yishai
authors: Y
authors: Levy
authors: Andrew P
authors: AP
authors: Levy
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D003176:Complement C3 / Q000378:metabolism; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D004311:Double-Blind Method; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D010084:Oxidation-Reduction; D010597:Pharmacogenetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D014810:Vitamin E / Q000627:therapeutic use*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D003176:Complement C3; D006242:Haptoglobins; D008054:Lipid Peroxides; D008075:Lipoproteins, HDL; D011956:Receptors, Cell Surface; D014810:Vitamin E