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

S Villette, J A M Kyle, K M Brown, Karen Pickard, J S Milne, F Nicol, John Arthur, J E 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. (C) 2002 Elsevier science (USA).

Original languageEnglish
Pages (from-to)174-178
Number of pages5
JournalBlood Cells, Molecules & Diseases
Volume29
Issue number2
DOIs
Publication statusPublished - Sep 2002

Keywords

  • selenium
  • phospholipid hydroperoxide glutathione peroxidase
  • GPX4
  • SNP
  • lipoxygenase metabolism
  • selenium deficiency
  • gene-expression

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