Variants in the genes encoding TNF-?, IL-10, and GSTP1 influence the effect of a-tocopherol on inflammatory cell responses in healthy men

England, Anna, Valdes, Ana M., Slater-Jefferies, Joanne L., Gill, Rosalynn, Howell, W. Martin, Calder, Philip C. and Grimble, Robert F. (2012) Variants in the genes encoding TNF-?, IL-10, and GSTP1 influence the effect of a-tocopherol on inflammatory cell responses in healthy men. American Journal of Clinical Nutrition, 95 (6), 1461-1467. (doi:10.3945/ajcn.111.012781). (PMID:22572643)

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 ?-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 ?-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) ?-tocopherol/d for 6 wk. The production of TNF-? and IL-1?, -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 ?-tocopherol to affect TNF-? production by LPS-stimulated PBMCs was influenced by the TNFA ?238 polymorphism (P = 0.016). The ability of ?-tocopherol to affect IL-6 production was influenced by the GSTP1 313 polymorphism (P = 0.019). The ability of ?-tocopherol to affect IL-1? 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 ?-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.

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Contributors

Author: Joanne L. Slater-Jefferies

Author: Philip C. Calder

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