Association between plasma selenium level and NRF2 target genes expression in humans

Animal studies in rodent and in vitro studies indicate compensatory role of nuclear factor (erythroid-derived 2)-like (Nrf2) and Nrf2-regulated antioxidant and phase II biotransformation enzymes for the dietary selenium (Se) deficiency or for the loss of selenoproteins.To explore associations between plasma Se level and NRF2-regulated cytoprotective genes expression, an observational study was conducted in a population of 96 healthy non-smoking men living in Central Poland aged 18–83 years with relatively low plasma Se level. NRF2, KEAP2, CAT, EPHX1, GCLC, GCLM, GPX2, GSR, GSTA1, GSTM1, GSTP1, GSTT1, HMOX1, NQO1, PRDX1, SOD1, SOD2, TXNRD1 transcript levels in peripheral blood leukocytes and polymorphism of NRF2-617C/A (rs6721961) in blood genomic DNA were determined by means of quantitative real-time PCR.Mean plasma Se level was found to be 51.10 ± 15.25 μg/L (range 23.86–96.18 μg/L). NRF2 mRNA level was positively correlated with expression of investigated NRF2-target genes. The multivariate linear regression adjusting for selenium status showed that plasma Se level was significantly inversely associated only with expression of GSTP1 (β-coef. = −0.270, p = 0.009), PRDXR1 (β-coef. = −0.245, p = 0.017) and SOD2 with an inverse trend toward significance (β-coef. = −0.186, p = 0.074), but without an effect of NRF2 gene variants. NRF2 expression was inversely associated with age (r = −0.23, p = 0.03) and body mass index (r = −0.29, p < 0.001). The findings may suggest a possible link between plasma Se level and cytoprotective response at gene level in humans.