Relative Abundance of Selenoprotein P Isoforms in Human Plasma Depends on Genotype, Se Intake, and Cancer Status

Catherine Meplan, Fergus Nicol, Brian T. Burtle, Lynne Kathryn Crosley, John Arthur, John C. Mathers, John E. Hesketh

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Selenium ( Se), a dietary trace metal essential for human health, is incorporated into selenoproteins as selenocysteine. Selenoprotein P (SePP), the major plasma selenoprotein, has both transport and antioxidant functions. In humans, it exists in plasma as two isoforms of similar to 50 and 60 kDa. This study investigated the effect of polymorphisms in the SEPP-1 gene, Se supplementation, and disease status on the proportions of SePP plasma isoforms. SePP was isolated from plasma from healthy volunteers, before and after a 6-week supplementation with 100 mu g sodium selenite, and from colon cancer patients and controls. SePP isoform distribution was analysed by Western blot. In healthy volunteers, the relative abundance of each isoform depended on two SEPP-1 polymorphisms: rs3877899, predicted to cause an Ala-to-Thr amino acid change at position 234, and rs7579, located in the 3'-untranslated region of SEPP-1 mRNA. The difference between genotypes disappeared after Se supplementation. A genotype-dependent reduction was seen in the proportion of the 60-kDa isoform in patients with colorectal cancer compared with controls. We conclude that functional polymorphisms in the SEPP-1 gene influence the proportion of SePP isoforms in plasma. An elevated proportion of the 60-kDa isoform of SePP may increase selenoprotein synthesis and reduce colorectal cancer risk.

Original languageEnglish
Pages (from-to)2631-2640
Number of pages10
JournalAntioxidants & Redox Signaling
Volume11
Issue number11
Early online date12 Aug 2009
DOIs
Publication statusPublished - 15 Oct 2009

Keywords

  • open reading frame
  • selenium supplementation
  • colorectal adenoma
  • messenger-RNA
  • prevention
  • expression
  • risk
  • purification
  • involvement
  • tissues

Cite this

Meplan, C., Nicol, F., Burtle, B. T., Crosley, L. K., Arthur, J., Mathers, J. C., & Hesketh, J. E. (2009). Relative Abundance of Selenoprotein P Isoforms in Human Plasma Depends on Genotype, Se Intake, and Cancer Status. Antioxidants & Redox Signaling, 11(11), 2631-2640. https://doi.org/10.1089/ars.2009.2533