Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender‐specific manner (the SELGEN study)

  title={Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender‐specific manner (the SELGEN study)},
  author={Catherine Méplan and Lynne K. Crosley and Fergus Nicol and Geoffrey J. Beckett and Alexander F. Howie and Kristina E. Hill and Graham W. Horgan and John Cummings Mathers and John R. Arthur and John E. Hesketh},
  journal={The FASEB Journal},
  pages={3063 - 3074}
Selenium (Se), a micronutrient essential for human health, is incorporated into at least 25 selenoproteins including selenoprotein P (SePP)′ which transports Se within the body. This research identified two single nucleotide polymorphisms (SNPs) in the SePP gene, one in the coding region (position 24731, causing an Ala to Thr change) and one in the 3′untranslated region (position 25191). Their frequency was similar in Caucasian, Chinese, and South Asian populations. Prospectively geno‐typed… 

Genetic polymorphism in selenoprotein P modifies the response to selenium-rich foods on blood levels of selenium and selenoprotein P in a randomized dietary intervention study in Danes

This study indicates that genetically determined variation in SELENOP leads to different responses in expression of selenoproteins following consumption of seenium-rich foods.

Functional effects of a common single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene: interaction with sex.

The GPX4c718t SNP both alters protein binding to the 3'UTR in vitro and influences the concentration of lymphocyte GPx4 and other selenoproteins in vivo and, at low selenium intake, the SNP thus may influence susceptibility to disease.

Relative abundance of selenoprotein P isoforms in human plasma depends on genotype, se intake, and cancer status.

It is concluded that functional polymorphisms in the SEPP-1 gene influence the proportion of SePP isoforms in plasma and an elevated proportion of the 60-kDa isoform of Se PP may increase selenoprotein synthesis and reduce colorectal cancer risk.

Genetic polymorphisms in selenoprotein P gene affect colorectal, prostate and breast cancer risk

Two single nucleotide polymorphisms (SNP) that affect SePP plasma isoform pattern and expression of other selenoproteins were identified in the SEPP1 gene, suggesting that genotype for these twoSEPP1 variants affects cancer risk.

Genetically determined variations of selenoprotein P are associated with antioxidant, muscular, and lipid biomarkers in response to Brazil nut consumption by patients using statins

SNPs in SELENOP could be associated with interindividual differences in Se homeostasis after Brazil nut consumption, emphasising the involvement of genetic variability in response to Se consumption towards health maintenance and disease prevention.

Selenoprotein genes variants may modify the association between serum selenium and oral cancer risk.

It is suggested that serum Se levels may be significantly associated with oral cancer risk, yet the association may be modified by the effects of selenoprotein genes variants.

Influence of Genetic Variations in Selenoprotein Genes on the Pattern of Gene Expression after Supplementation with Brazil Nuts

Genetic variations in selenoprotein genes modulated both GPX1 and SELENOP selenobrotein gene expression and global gene expression in response to Brazil nut supplementation.

Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects.

The present results indicate that SEPP1 concentration is the best plasma biomarker studied for assessing optimal expression of all selenoproteins, because its optimization required a larger intake of selenium than did GPX activity.



Effects of Chemical Form of Selenium on Plasma Biomarkers in a High-Dose Human Supplementation Trial

Selenium in the form of selenomethionine is better absorbed than selenite, and plasma selenium concentration is useful in monitoring compliance and safety ofselenium supplementation as selenometrichionines but not as seenite.

Deletion of Selenoprotein P Alters Distribution of Selenium in the Mouse*

The results suggest that Se-P from liver provides selenium to several tissues, especially testis and brain, and indicate that transport forms of seenium other than Se-p exist because selenia levels of all tissues except testis responded to increases of dietary selenIUM in Sepp −/− mice.

Selenium-dependent pre- and posttranscriptional mechanisms are responsible for sexual dimorphic expression of selenoproteins in murine tissues.

Analysis of Se concentrations and expression levels of several selenoproteins including type I iodothyronine deiodinase (Dio1) and glutathione peroxidase (GPx) isozymes in male and female mice concluded that Se-dependent posttranscriptional mechanisms are operational that affect either translational efficiency or Dio1 stability in a sex- and tissue-specific manner.

Effects of organic and inorganic selenium supplementation on selenoenzyme activity in blood lymphocytes, granulocytes, platelets and erythrocytes.

The different and contrasting effects that Se supplementation had on blood selenoenzyme activities may be indicative of a difference in metabolic need for Se regulated at the level of Se-dependent cell function.

Effectiveness of selenium supplements in a low-selenium area of China.

It is suggested that selenoprotein P is a better indicator of selenium nutritional status than is glutathione peroxidase and that the recommended dietary allowance of Selenium, which was set with the use of glutathion peroxIDase as the index of seenium status, should be revised.

Hepatically derived selenoprotein P is a key factor for kidney but not for brain selenium supply.

It is shown that a transport function in plasma is exerted by hepatically derived SePP, while in brain SePP fulfils a second, hitherto unexpected, essential role.

Neurological dysfunction occurs in mice with targeted deletion of the selenoprotein P gene.

This study shows that neurological dysfunction occurs when selenium supply to the brain is curtailed and that the dysfunction is not readily reversible, indicating that selenoprotein P and at least one other form of selenum supply the element to thebrain.

An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status.

The data indicate that these subjects had a functional selenium deficit with suboptimal immune status and a deficit in viral handling, and suggest that the additional 100 microg Se/d may be insufficient to support optimal function.

Selenium and its relationship to cancer: an update†

Even though SeMCYS was shown to be the most effective seleno-compound in the reduction of mammary tumours, it may not be the best choice for reduction of colon tumours because several mechanisms have been proposed on the mechanism whereby Se reduces tumours.

The importance of selenium to human health