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Lookup NU author(s): Dr Catherine Meplan, Brian Burtle, Professor John Mathers, Professor John Hesketh
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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. Antioxid. Redox Signal. 11, 2631-2640.
Author(s): Meplan C, Nicol F, Burtle BT, Crosley LK, Arthur JR, Mathers JC, Hesketh JE
Publication type: Article
Publication status: Published
Journal: Antioxidants & Redox Signaling
Year: 2009
Volume: 11
Issue: 11
Pages: 2631-2640
ISSN (print): 1523-0864
ISSN (electronic): 1557-7716
Publisher: Mary Ann Liebert, Inc. Publishers
URL: http://dx.doi.org/10.1089/ars.2009.2533
DOI: 10.1089/ars.2009.2533
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