Wednesday, September 19, 2012

Variants in the genes encoding TNF-α, IL-10, and GSTP1 influence the effect of α-tocopherol on inflammatory cell responses in healthy men1,2,3

  1. Robert F Grimble
+ Author Affiliations
  1. 1From the Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, IDS Building, Southampton General Hospital, Southampton, United Kingdom (AE, JLS-J, PCC, and RFG); the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (AMV); SomaLogic Inc, Boulder, CO (RG); and the Department of Histocompatibility and Immunogenetics, National Health Service Blood and Transplant, Newcastle upon Tyne, United Kingdom (WMH).
+ Author Notes
  • ↵2 Supported by the Biotechnology and Biological Sciences Research Council and Sciona under the Agri-Food LINK scheme. α-Tocopherol was a gift from Lamberts Healthcare.
  • ↵3 Address correspondence to PC Calder, Institute of Developmental Sciences Building, Faculty of Medicine, University of Southampton, MP 887, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom. E-mail: pcc@soton.ac.uk.

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.
Design: 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.
  • Received January 25, 2012.
  • Accepted February 9, 2012.
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