title: Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study).
abstract: Selenium (Se), a micronutrient essential for human health, is incorporated into at least 25 selenoproteins including selenoprotein P (SePP), which transports Se within the body. This research identified two single nucleotide polymorphisms (SNPs) in the SePP gene, one in the coding region (position 24731, causing an Ala to Thr change) and one in the 3'untranslated region (position 25191). Their frequency was similar in Caucasian, Chinese, and South Asian populations. Prospectively genotyped volunteers were supplemented for 6 wk with 100 microg sodium selenite/day. Blood samples were analyzed for plasma Se and selenoprotein biomarkers at baseline, after supplementation, and during a washout period. Plasma Se, SePP, and glutathione peroxidase 3 (GPx3) levels increased with supplementation. Baseline plasma Se content depended on both SePP genotypes and body mass index. Presupplementation SePP concentration was associated with gender and genotype at SNP 24731 and postsupplementation concentration with SNP 25191. Both SNPs and gender were associated with differences in GPx3 activity, plasma, and erythrocyte thioredoxin reductase 1 concentrations and lymphocyte glutathione peroxidase 1 and 4 activities and concentrations. In conclusion, the data reveal two common functional SNPs within the human SePP gene that may predict behavior of biomarkers of Se status and response to supplementation and thus susceptibility to disease.
authors.affiliation: Institute for Cell and Molecular Biosciences and Human Nutrition Research Centre, The Medical School, Newcastle University, Newcastle-upon-Tyne, NE2 4HH UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Méplan
authors.forename: Lynne K
authors.initials: LK
authors.lastname: Crosley
authors.forename: Fergus
authors.initials: F
authors.lastname: Nicol
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Beckett
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Howie
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Hill
authors.forename: Graham
authors.initials: G
authors.lastname: Horgan
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
authors.forename: John R
authors.initials: JR
authors.lastname: Arthur
authors.forename: John E
authors.initials: JE
authors.lastname: Hesketh
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D001773:Blood Cells / Q000378:metabolism; D019587:Dietary Supplements; D004198:Disease Susceptibility; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005838:Genotype; D005979:Glutathione Peroxidase / Q000097:blood / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation; D012643:Selenium / Q000008:administration & dosage / Q000378:metabolism; D051149:Selenoprotein P / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D006113:United Kingdom; D000094765:Glutathione Peroxidase GPX1
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D051149:Selenoprotein P; C506030:TNFRSF11B protein, human; C486484:GPX3 protein, human; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human