title: Genetic variation in GPX1 is associated with GPX1 activity in a comprehensive analysis of genetic variations in selenoenzyme genes and their activity and oxidative stress in humans.
abstract: Previous studies suggest some effects of selenium on risk of several chronic diseases, which may be mediated through a small number of selenoenzymes with antioxidant properties. In this cross-sectional analysis of 195 participants from the Seattle Barrett's Esophagus Study who were free of esophageal cancer at the time of blood draw, we examined whether the number of the minor alleles in 26 tagging single nucleotide polymorphisms (SNP) of five selenoenzyme genes [i.e., glutathione peroxidase 1-4 (GPX1-4) and selenoprotein P (SEPP1)] was associated with activity of GPX1 in white blood cells and GPX3 in plasma, and concentrations of SEPP1 and markers of oxidative stress [malondialdehyde (MDA) and protein carbonyl content] in plasma. At the gene level, associations were observed between overall variation in GPX1 and GPX1 activity (P = 0.02) as well as between overall variation in GPX2 and SEPP1 concentrations (P = 0.03). By individual SNP, two variants in GPX1 (rs8179164 and rs1987628) showed a suggestive association with GPX1 activity (P = 0.10 and 0.08, respectively) and two GPX2 variants (rs4902346 and rs2071566) were associated with SEPP1 concentration (P = 0.004 and 0.002, respectively). Furthermore, two SNP in the SEPP1 gene (rs230813 and rs230819) were associated with MDA concentrations (P = 0.03 and 0.02, respectively). Overall, our study supports the hypothesis that common genetic variants in selenoenzymes affect their activity.
authors.affiliation: Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Yumie
authors.initials: Y
authors.lastname: Takata
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Burk
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Hill
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.forename: Alan R
authors.initials: AR
authors.lastname: Kristal
authors.forename: David J
authors.initials: DJ
authors.lastname: Duggan
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
mesh_terms: D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics* / Q000502:physiology*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D020641:Polymorphism, Single Nucleotide; D050050:Protein Carbonylation / Q000235:genetics; D012307:Risk Factors; D012643:Selenium / Q000378:metabolism; D051149:Selenoprotein P / Q000097:blood / Q000235:genetics; D000094765:Glutathione Peroxidase GPX1
chemical_list: D051149:Selenoprotein P; D008315:Malondialdehyde; C117436:GPX2 protein, human; C486484:GPX3 protein, human; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human