DNA damage and oxidative stress response to selenium yeast in the non-smoking individuals: a short-term supplementation trial with respect to GPX1 and SEPP1 polymorphism

Abstract

PurposeSelenium, both essential and toxic element, is considered to protect against cancer, though human supplementation trials have generated many inconsistent data. Genetic background may partially explain a great variability of the studies related to selenium and human health. The aim of this study was to assess whether functional polymorphisms within two selenoprotein-encoding genes modify the response to selenium at the level of oxidative stress, DNA damage, and mRNA expression, especially in the individuals with a relatively low selenium status.MethodsThe trial involved 95 non-smoking individuals, stratified according to GPX1 rs1050450 and SEPP1 rs3877899 genotypes, and supplemented with selenium yeast (200 µg) for 6 weeks. Blood was collected at four time points, including 4 weeks of washout.ResultsAfter genotype stratification, the effect of GPX1 rs1050450 on lower GPx1 activity responsiveness was confirmed; however, in terms of DNA damage, we failed to indicate that individuals homozygous for variant allele may especially benefit from the increased selenium intake. Surprisingly, considering gene and time interaction, GPX1 polymorphism was observed to modify the level of DNA strand breaks during washout, showing a significant increase in GPX1 wild-type homozygotes. Regardless of the genotype, selenium supplementation was associated with a selectively suppressed selenoprotein mRNA expression and inconsistent changes in oxidative stress response, indicating for overlapped, antioxidant, and prooxidant effects. Intriguingly, DNA damage was not influenced by supplementation, but it was significantly increased during washout.ConclusionsThese results point to an unclear relationship between selenium, genotype, and DNA damage.Electronic supplementary materialThe online version of this article (doi:10.1007/s00394-015-1118-4) contains supplementary material, which is available to authorized users.

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

“…As for the influence of diet, none of the individuals reported a change to his/her dietary habits during the trial. The second major weakness of this study is attributable to the fact that the trial was not randomized (subjects were selected for the study according to genotype) and not placebo controlled (for details see [22]). Since no separate control group was investigated, we compared all data with respect to baseline values, measured on the first day of the trial, before taking the first pill with the supplement.…”

“…Details of the trial, as well as subjects’ exclusion criteria, were described elsewhere [22]. The exclusion criteria for subjects’ recruitment included inter alia current smoking and self-reported prevalence of diabetes.…”

“…Table 1 presents basic characteristics of the subjects. Plasma Se concentration was measured previously (as described in [22]) and mean plasma Se levels calculated for 76 subjects at each time points are presented also in Table 1.…”

“…The description of material preservation, mRNA isolation, quantification, and quality assessment were described previously [22]. For reverse transcription we used a QuantiTect Kit (Qiagen, Hilden, Germany).…”

Genetic variants in selenoprotein genes modulate biomarkers of selenium status in response to Brazil nut supplementation (the SU.BRA.NUT study)

“…Nevertheless, human studies have failed to demonstrate an association between Se status and selenoprotein transcripts [14][15][16] . Only three studies have observed a positive association between Se supplementation and increased selenoprotein expression in humans (SELENOF, SELENOK, GPX1 and SELENOP) 13,17,18 .…”