title: A novel single nucleotide polymorphism in the 3' untranslated region of human glutathione peroxidase 4 influences lipoxygenase metabolism.
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.
authors.affiliation: Department of Biological and Nutritional Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU United Kingdom.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Villette
authors.forename: Janet A M
authors.initials: JA
authors.lastname: Kyle
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Brown
authors.forename: Karen
authors.initials: K
authors.lastname: Pickard
authors.forename: John S
authors.initials: JS
authors.lastname: Milne
authors.forename: Fergus
authors.initials: F
authors.lastname: Nicol
authors.forename: John R
authors.initials: JR
authors.lastname: Arthur
authors.forename: John E
authors.initials: JE
authors.lastname: Hesketh
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008875:Middle Aged; D009690:Nucleic Acid Conformation; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry; D012643:Selenium / Q000097:blood; D051140:Selenoproteins
chemical_list: D020413:3' Untranslated Regions; D011506:Proteins; D012333:RNA, Messenger; D051140:Selenoproteins; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D001094:Arachidonate 5-Lipoxygenase; D012643:Selenium