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

• Published in: The American journal of clinical nutrition Vol. 95; no. 6; p. 1461
• Main Authors: England, Anna, Valdes, Ana M, Slater-Jefferies, Joanne L, Gill, Rosalynn, Howell, W Martin, Calder, Philip C, Grimble, Robert F
• Format: Journal Article
• Language: English
• Published: Bethesda American Society for Clinical Nutrition, Inc 01-06-2012
• Subjects: Cells; Cytokines; Dietary supplements; Genes; Mens health; Vitamin E
• ISSN: 0002-9165; 1938-3207

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. 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. 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. 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-1βproduction was influenced by the IL10 -592 and -1082 polymorphisms (P = 0.025 and P = 0.016, respectively). 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.