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

Purpose: Selenium, 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.

Methods: The 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.

Results: After 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.

Conclusions: These results point to an unclear relationship between selenium, genotype, and DNA damage.

Keywords: DNA damage; Gene expression; Oxidative stress; Selenium; Selenium supplementation; Selenoproteins.

Fig. 1

a GPX1 rs1050450 effect on GPx1 activity in the individuals supplemented with selenium. A significant SNP effect was observed regardless of time. Data adjusted for age, sex, BMI, and baseline selenium; b mean GPx1 activity increase after 6 weeks of supplementation, with respect to GPX1 genotype. Data adjusted for age, sex, BMI, and baseline GPx1 activity. p values for the ANCOVA/MANCOVA and contrast tests indicated in the figures

Fig. 2

GPX1 rs1050450 effect on GPx3 activity in the individuals supplemented with selenium. A significant SNP effect was observed in the interaction with time. Data adjusted for age, sex, BMI, and baseline selenium. p values for the MANCOVA indicated in the figure. According to the particular time points analysis, a significant difference in GPx3 activity as compared to baseline was shown after 6 weeks of supplementation and during the washout period for ProPro (p < 0.0001 and p = 0.002, respectively) and ProLeu (p = 0.001 and p = 0.02, respectively)

Fig. 3

GPX1 rs1050450 effect on DNA oxidation (expressed as % of DNA in comet tail) in the individuals supplemented with selenium. A significant SNP effect was observed regardless of time. Data adjusted for age, sex, BMI, and baseline selenium. p values for the MANCOVA and contrast test indicated in the figure

Fig. 4

GPX1 rs1050450 effect on DNA strand breaks (expressed as % of DNA in comet tail) in the individuals supplemeted with selenium. A significant SNP effect was observed in the interaction with time. Data adjusted for age, sex, BMI, and baseline selenium. p values for the MANCOVA indicated in the figure. According to the particular time point analysis, a significant difference in DNA strand breaks as compared to baseline was shown during washout for ProPro homozygotes, p < 0.0001

Fig. 5

SEPP1 rs3877899 effect on SOD1 activity in the individuals supplemented with selenium. A significant SNP effect was observed in the interaction with time. Data adjusted for age, sex, BMI, and baseline selenium. p values for the MANCOVA indicated in the figure. According to the particular time point analysis, a significant difference in GPx3 activity as compared to baseline was shown for AlaAla homozygotes during washout (p = 0.04)