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Published Online: 15 October 2009

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

Publication: Antioxidants & Redox Signaling
Volume 11, Issue Number 11

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 ∼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 μg 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. Antioxid. Redox Signal. 11, 2631–2640.

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Information & Authors

Information

Published In

cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 11Issue Number 11November 2009
Pages: 2631 - 2640
PubMed: 19453253

History

Published in print: November 2009
Published online: 15 October 2009
Published ahead of print: 12 August 2009
Published ahead of production: 19 May 2009
Accepted: 19 May 2009
Revision received: 28 April 2009
Received: 24 February 2009

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Affiliations

Catherine Méplan
Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle, England.
Human Nutrition Research Centre, The Medical School, Newcastle University, Newcastle, England.
Fergus Nicol
Rowett Institute of Nutrition and Health, Aberdeen University, Bucksburn, Aberdeen, Scotland.
Brian T. Burtle
Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle, England.
Human Nutrition Research Centre, The Medical School, Newcastle University, Newcastle, England.
Lynne K. Crosley
Rowett Institute of Nutrition and Health, Aberdeen University, Bucksburn, Aberdeen, Scotland.
John R. Arthur
Rowett Institute of Nutrition and Health, Aberdeen University, Bucksburn, Aberdeen, Scotland.
John C. Mathers
Human Nutrition Research Centre, The Medical School, Newcastle University, Newcastle, England.
Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle, England.
John E. Hesketh
Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle, England.
Human Nutrition Research Centre, The Medical School, Newcastle University, Newcastle, England.

Notes

Address correspondence to:
John E. Hesketh
Institute for Cell and Molecular Biosciences
Human Nutrition Research Centre
The Medical School
Newcastle University
NE2 4HH Newcastle, UK
E-mail: [email protected]

Author Disclosure Statement

No competing financial interests exist.

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