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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #234033

Title: Polymorphisms at cytokine genes may determine the effect of vitamin E on cytokine production in the elderly

Author
item BELISLE, SARAH - JM USDA HNRCA @ TUFTS
item LEKA, LYNETTE - JM USDA HNRCA @ TUFTS
item LISTA, JAVIER DELGADO - HOSPITAL UNIV REINA SOFIA
item Jacques, Paul
item Ordovas, Jose
item Meydani, Simin

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/31/2009
Publication Date: 10/1/2009
Citation: Belisle, S.E., Leka, L.S., Lista, J., Jacques, P., Ordovas, J.M., Meydani, S. 2009. Polymorphisms at cytokine genes may determine the effect of vitamin E on cytokine production in the elderly. Journal of Nutrition. 139:1855-1860.

Interpretive Summary: When the body has an infection, it produces proteins called cytokines that help the body resist the infection. With age, the body is less able to fight off infections. Vitamin E supplements have been suggested to improve the body’s ability to fight off infection. The improvements with vitamin E supplements may be from the effect of vitamin E on cytokines. However, not all elderly individuals that take vitamin E supplements have the same improvement in response to infection. In younger people, genetic differences between people influence cytokine production. We tested if these common genetic differences explained why the effect of vitamin E on cytokines varied from person to person in the elderly. To test this, we used information on cytokine production, genetic background from a group of elderly people who were given vitamin E supplements for one year and a group given a placebo for a year. We looked specifically at cytokines names IL-1beta, IL-6 and TNF-alpha. There was not a significant difference in cytokine levels before supplementation when people with common genetic changes were compared. Overall, those people who received vitamin E supplements did not have different levels of cytokines. However, we observed that a common genetic difference located at the cytokine named TNF-alpha may affect how vitamin E supplements alter TNF-alpha production in those elderly people. These observations indicate the effect of vitamin E on some cytokines in elderly people may be influenced by common genetic differences. The information from our study adds to the body of knowledge that will eventually help us determine why vitamin E does not affect all people the same way. Such knowledge will help us determine which elderly people might benefit the most from taking vitamin E supplements.

Technical Abstract: Cytokines play an important role in regulating immune response to infection. Vitamin E has been noted to impact cytokine production. However, individual response to vitamin E supplementation varies. Previous studies indicate that cytokine production is heritable, and common single nucleotide polymorphisms (SNPs) may explain differences in cytokine production between individuals. We hypothesize that the differential response to the immunomodulatory actions of vitamin E reflects genetic differences among individuals including SNPs at cytokine genes that modulate cytokine production. We used data from a double-blind, placebo-controlled vitamin E intervention study in an elderly sample to test this hypothesis. We observed that the effect of vitamin E on TNF-alpha production is dependent on TNF-308G>A. Subjects with the G/G genotype at TNF- alpha -308G>A who were treated with vitamin E had higher TNF- alpha production compared to subjects with the G/G genotype treated with placebo. In contrast, subjects with the A/A and A/G genotype at TNF- alpha -308G>A who were treated with vitamin E had lower TNF- alpha production compared to subjects with the A allele treated with placebo. This observation suggests that individual immune response to vitamin E supplementation is in part mediated by genetic factors. Since the A allele at TNF- alpha has been previously associated with higher TNF- alpha levels, our observations may indicate that anti-inflammatory effect of vitamin E is specific to those genetically predisposed to higher inflammation. Further studies will be needed to determine the biological mechanism driving the interaction between vitamin E treatment and TNF- alpha -308G>A, and its implications for disease resistance.