Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases the expression of lymphocyte protein biosynthesis genes

Background: Selenium is incorporated into 25 selenoproteins in humans. Low dietary selenium has deleterious effects on health and may result in cancer, cardiovascular disease, and immune dysfunction. The underlying mechanisms are not fully understood. Lymphocytes are a target tissue; they can be assessed in healthy persons, and their response has not been explored by using global gene expression profiling techniques. Objectives: The objectives of the study were to assess the overall effect of selenium supplementation within a normal physiological range on the pattern of lymphocyte gene expression and to identify downstream processes affected by selenium intake. Design: Gene expression was assessed in lymphocytes isolated from 39 healthy persons before and after a 6-wk supplementation with 100 eta g Se/d as sodium selenite. Presupplementation and postsupplementation RNA samples from 16 subjects were chosen at random for microarray analysis. Differential gene expression was analyzed by using individual labeling and hybridization with human whole-genome microarrays. Array data were validated by quantitative real-time reverse transcriptase-polymerase chain reaction. Results: The study subjects had an average 19% increase in plasma selenium concentration, which was within a normal range. Fold changes in gene expression were small, but data analysis using biological process identification showed that selenium predominantly affected the genes that encode proteins functioning in protein biosynthesis. Gene expression changes were confirmed by quantitative polymerase chain reaction for 3 representative target genes (RPL37A, RPL30, and EEF1E1). Conclusions: Ribosomal protein and translation factor genes were up-regulated in response to increased selenium intake. We hypothesize that this up-regulation is linked to increased selenoprotein production and enhanced lymphocyte function.