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)

Catherine Méplan, Lynne K. Crosley, Fergus Nicol, Geoffrey J. Beckett, Alexander F. Howie, Kristina E. Hill, Graham Horgan, John C. Mathers, John Arthur, John E. Hesketh

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Abstract

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 genotyped volunteers were supplemented for 6 wk with 100 mu g sodium selenite/ day. Blood samples were analyzed for plasma Se and selenoprotein biomarkers at baseline, after supplementation, and during a washout period. Plasma Se, SePP, and glutathione peroxidase 3 (GPx3) levels increased with supplementation. Baseline plasma Se content depended on both SePP genotypes and body mass index. Pre-supplementation SePP concentration was associated with gender and genotype at SNP 24731 and post-supplementation concentration with SNP 25191. Both SNPs and gender were associated with differences in GPx3 activity, plasma, and erythrocyte thioredoxin reductase 1 concentrations and lymphocyte glutathione peroxidase 1 and 4 activities and concentrations. In conclusion, the data reveal two common functional SNPs within the human SePP gene that may predict behavior of biomarkers of Se status and response to supplementation and thus susceptibility to disease.

Original languageEnglish
Pages (from-to)3063-3074
Number of pages12
JournalThe FASEB Journal
Volume21
Issue number12
Early online date29 May 2007
DOIs
Publication statusPublished - 1 Oct 2007

Keywords

  • nutrient-gene interaction
  • 3 ' untranslated region
  • BMI
  • glutathione-peroxidase
  • cancer prevention
  • oxidative damage
  • expression
  • health
  • deficiency
  • mortality
  • deletion
  • tissues
  • mouse

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