title: Variants in the genes encoding TNF-α, IL-10, and GSTP1 influence the effect of α-tocopherol on inflammatory cell responses in healthy men.
abstract: BACKGROUND
  Despite evidence of antioxidant effects of vitamin E in vitro and in animal studies, large, randomized clinical trials have not substantiated a benefit of vitamin E in reducing inflammation in humans. An individual's genetic background may affect the response to α-tocopherol supplementation, but this has rarely been investigated.
  
  
  OBJECTIVE
  The aim of this study was to explore the role of genetic polymorphisms on changes in LPS-stimulated inflammatory cytokine production from peripheral blood mononuclear cells (PBMCs) after α-tocopherol supplementation.
  
  
  METHODS
  A total of 160 healthy, middle-aged male volunteers (mean age: 52.7 y) were given dietary supplements of either 75 IU (low dose; n = 57) or 600 IU (high dose; n = 103) α-tocopherol/d for 6 wk. The production of TNF-α and IL-1β, -6, and -10 by PBMCs after LPS stimulation was measured at baseline and after 6 wk. Polymorphisms in 15 genes involved in inflammation or responses to oxidative stress were characterized in the subjects.
  
  
  RESULTS
  The ability of α-tocopherol to affect TNF-α production by LPS-stimulated PBMCs was influenced by the TNFA -238 polymorphism (P = 0.016). The ability of α-tocopherol to affect IL-6 production was influenced by the GSTP1 313 polymorphism (P = 0.019). The ability of α-tocopherol to affect IL-1β production was influenced by the IL10 -592 and -1082 polymorphisms (P = 0.025 and P = 0.016, respectively).
  
  
  CONCLUSIONS
  In healthy control subjects, the effect of α-tocopherol supplementation on the production of inflammatory cytokines appears to be dependent on an individual's genotype. These genotype-specific differences may help explain some of the discordant results in studies that used vitamin E.
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, IDS Building, Southampton General Hospital, Southampton, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: England
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Slater-Jefferies
authors.forename: Rosalynn
authors.initials: R
authors.lastname: Gill
authors.forename: W Martin
authors.initials: WM
authors.lastname: Howell
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
authors.forename: Robert F
authors.initials: RF
authors.lastname: Grimble
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019587:Dietary Supplements; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D051549:Glutathione S-Transferase pi; D024502:alpha-Tocopherol