Effects of Selenium Supplementation on Selenoprotein Gene Expression and Response to Influenza Vaccine Challenge: A Randomised Controlled Trial

Background: The uncertainty surrounding dietary requirements for selenium (Se) is partly due to limitations in biomarkers of Se status that are related to health outcomes. In this study we determined the effect of different doses and forms of Se on gene expression of selenoprotein S (SEPS1), selenoprotein W (SEPW1) and selenoprotein R (SEPR), and responses to an immune function challenge, influenza vaccine, were measured in order to identify functional markers of Se status. Methods and Findings: A 12 week human dietary intervention study was undertaken in 119 volunteers who received placebo, 50, 100 or 200 mu g/day Se-enriched yeast (Se-yeast) or meals containing unenriched or Se-enriched onions (50 mu g/day). Gene expression was quantified in RNA samples extracted from human peripheral blood mononuclear cells (PBMC's) using quantitative RT-PCR. There was a significant increase in SEPW1 mRNA in the Se-enriched onion group (50 mu g/day) compared with the unenriched onion group. SEPR and SEPW1 did not change significantly over the duration of the supplementation period in the control or Se-yeast groups, except at week 10 when SEPW1 mRNA levels were significantly lower in the 200 mg/day Se-yeast group compared to the placebo group. Levels of SEPS1 mRNA increased significantly 7 days after the influenza vaccine challenge, the magnitude of the increase in SEPS1 gene expression was dose-dependent, with a significantly greater response with higher Se supplementation. Conclusions: This novel finding provides preliminary evidence for a role of SEPS1 in the immune response, and further supports the relationship between Se status and immune function.