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

Variants in the genes encoding TNF-?, IL-10, and GSTP1 influence the effect of a-tocopherol on inflammatory cell responses in healthy men
Variants in the genes encoding TNF-?, IL-10, and GSTP1 influence the effect of a-tocopherol on inflammatory cell responses in healthy men
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.
0002-9165
1461-1467
England, Anna
590a306a-2173-4799-80b8-d09e44854f59
Valdes, Ana M.
4e4c3f14-3895-4129-94ca-f4176dd83e94
Slater-Jefferies, Joanne L.
e46c711a-9d4c-436a-b853-828df69bb4d7
Gill, Rosalynn
9773f903-e825-4946-b198-3e9485ad05f7
Howell, W. Martin
ecbb0dd6-f904-4da2-a05d-e542862531f8
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Grimble, Robert F.
3100e4d2-8f29-4ca6-a95d-38a6a764865f
England, Anna
590a306a-2173-4799-80b8-d09e44854f59
Valdes, Ana M.
4e4c3f14-3895-4129-94ca-f4176dd83e94
Slater-Jefferies, Joanne L.
e46c711a-9d4c-436a-b853-828df69bb4d7
Gill, Rosalynn
9773f903-e825-4946-b198-3e9485ad05f7
Howell, W. Martin
ecbb0dd6-f904-4da2-a05d-e542862531f8
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Grimble, Robert F.
3100e4d2-8f29-4ca6-a95d-38a6a764865f

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)

Record type: Article

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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More information

e-pub ahead of print date: 9 May 2012
Published date: June 2012
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 339925
URI: http://eprints.soton.ac.uk/id/eprint/339925
ISSN: 0002-9165
PURE UUID: a4d4133a-4044-4bf8-a769-c99d201bea92
ORCID for Joanne L. Slater-Jefferies: ORCID iD orcid.org/0000-0001-8325-1320
ORCID for Philip C. Calder: ORCID iD orcid.org/0000-0002-6038-710X

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Date deposited: 01 Jun 2012 13:59
Last modified: 15 Mar 2024 03:25

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Contributors

Author: Anna England
Author: Ana M. Valdes
Author: Rosalynn Gill
Author: W. Martin Howell
Author: Robert F. Grimble

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