Pro198Leu polymorphism affects the selenium status and GPx activity in response to Brazil nut intake

Abstract

Selenoproteins play important roles in antioxidant mechanisms, and are thus hypothesised to have some involvement in the pathology of certain types of dementia. Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are both thought to involve impaired biological activity of certain selenoproteins. Previously, supplementation with a selenium-rich Brazil nut (Bertholletia excelsa) has shown potential in reducing cognitive decline in MCI patients, and could prove to be a safe and effective nutritional approach early in the disease process to slow decline. Here, we have conducted a pilot study that examined the effects of a range of single nucleotide polymorphisms (SNPs) in genes encoding the selenoproteins glutathione peroxidase (GPX1) and selenoprotein P (SEPP) in response to selenium supplementation via dietary Brazil nuts, including selenium status, oxidative stress parameters and GPX1 and SEPP gene expression. Our data suggest that GPX1 Pro198Leu rs1050450 genotypes may differentially affect the selenium status and GPx activity. Moreover, rs7579 and rs3877899 SNPs in SEPP gene, as well as GPX1 rs1050450 genotypes can influence the expression of GPX1 and SEPP mRNA in response to Brazil nuts intake. This small study gives cause for larger investigations into the role of these SNPs in both the selenium status and response to selenium dietary intake, especially in chronic degenerative conditions like MCI and AD.

Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for Precision Nutrition Involving the Prevention and Management of Chronic Diseases Associated with Obesity

“…Furthermore, it was found that changes in plasma triglycerides in response to omega-3 fatty acid supplementation could be modulated by the effect of polymorphisms and DNA methylation on expression levels of key genes identified by genome-wide association studies [104]. Additionally, genetic variants in genes encoding the selenoproteins glutathione peroxidase ( GPX1 ) and selenoprotein P ( SEPP ) could influence their gene expressions in response to supplementation with a selenium-rich Brazil nut, suggesting a possible role in the nutritional treatment of chronic degenerative conditions [105]. …”

Influence of different genotypes in the pattern of selenoprotein expression in response to Brazil nut supplementation

“…No difference was observed in T-carriers. This genetic variation was associated with increased GPX1 mRNA expression in other Brazilian work conducted with Alzheimer's patients, but the authors found the increase in T-carriers instead of CC (CARDOSO et al, 2015a). Although some studies have investigated the association of this variation with differences on GPx1 activity JABLONSKA et al, 2009), few studies have associated this variation with GPX1 gene expression.…”

“…Alzheimer's patients also found an increase in GPX1 mRNA expression after supplementation with 1 unit of Brazil nut for 6 months (CARDOSO et al, 2015a). A possible explanation for this variation in response to Se supplementation is the presence of genetic variants, which most of the aforementioned works have not considered.…”

“…GPx1 activity and erythrocyte Se concentrations have been used in several studies as biomarkers of Se status that respond to Se supplementation via Brazil nuts (CARDOSO et al, 2015a;THOMSON et al, 2008). Erythrocyte Se correlates strongly with plasma Se.…”

“…Nevertheless, human studies have failed to demonstrate an association of Se status and selenoproteins transcripts (RAVN-HAREN et al, 2008a, 2008bSUNDE et al, 2008). Only two studies have observed a positive relationship between Se supplementation and increased selenoprotein expression (CARDOSO et al, 2015a;.…”