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A novel single nucleotide polymorphism in the 3′ untranslated region of human glutathione peroxidase 4 influences lipoxygenase metabolism

Lookup NU author(s): Dr Stephane Villette, Professor John Hesketh

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Abstract

Selenium (Se) is an essential micronutrient for human health. The biological roles of the essential micronutrient Se are attributed to its presence in a range of 20-30 selenoproteins including the cytosolic and phospholipid hydroperoxide glutathione peroxidases (GPX1 and GPX4). It has been suggested that GPX4 may play a role in regulation of leukotriene biosynthesis and thus inflammation. In eukaryotes Se is incorporated into selenoproteins as the amino acid selenocysteine in a process requiring a stem-loop within the 3′ untranslated region (3′UTR) of the mRNA. In this study the region of the GPX4 gene corresponding to the 3′UTR was scanned for mutations in a group of 66 volunteers. The data show a T/C variant at position 718. The distribution of this SNP in our population was 34% CC, 25% TT and 41% TC; i.e., it is in Hardy-Weinberg equilibrium. Individuals of different genotypes exhibited significant differences in the levels of lymphocyte 5-lipoxygenase total products, with C718 showing increased levels of those products compared to T718 and T/C718 (36% and 44% increases, respectively). The data suggest that the SNP718 that we have identified has functional effects and support the hypothesis that GPX4 plays a regulatory role in leukotriene biosynthesis. © 2002 Elsevier Science (USA).


Publication metadata

Author(s): Hesketh JE; Villette S; Kyle JAM; Brown KM; Pickard K; Milne JS; Nicol F; Arthur JR

Publication type: Article

Publication status: Published

Journal: Blood Cells, Molecules, and Diseases

Year: 2002

Volume: 29

Issue: 2

Pages: 174-178

ISSN (print): 1079-9796

ISSN (electronic): 1096-0961

Publisher: Academic Press

URL: http://dx.doi.org/10.1006/bcmd.2002.0556

DOI: 10.1006/bcmd.2002.0556

PubMed id: 12490284


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