title: Influence of the glutathione peroxidase 1 Pro200Leu polymorphism on the response of glutathione peroxidase activity to selenium supplementation: a randomized controlled trial.
abstract: BACKGROUND
  A genetic variant at codon 200 (Pro200Leu) of the gene encoding for glutathione peroxidase 1 (GPx1), a selenium-dependent enzyme, is associated with lower enzyme activity; however, the evidence is limited to in vitro and observational studies.
  
  
  OBJECTIVE
  The objective was to determine whether the GPx1 Pro200Leu genetic variants modify the response of whole-blood glutathione peroxidase (GPx) activity to selenium supplementation in patients with coronary artery disease in New Zealand.
  
  
  METHODS
  The results from 2 parallel-design, double-blind trials were combined. Participants were randomly assigned to receive a daily supplement of 100 μg Se as l-selenomethionine (n = 129) or placebo (n = 126) for 12 wk. Plasma selenium and whole-blood GPx activity were measured at baseline and at week 12. Participants were genotyped for the GPx1 Pro200Leu polymorphism.
  
  
  RESULTS
  Selenium supplementation increased whole-blood GPx activity by 5 (95% CI: 4, 7) U/g hemoglobin (P < 0.001); however, the magnitude of the increase did not differ by genotype (P = 0.165 for treatment-by-genotype interaction). In an exploratory analysis, a significant nutrient-gene interaction was apparent when baseline plasma selenium concentrations were included in the regression model (P = 0.006 for treatment-by-genotype × baseline selenium concentration interaction). Increases in GPx activity were 2-fold higher in Pro homozygotes than in participants carrying a Leu allele when baseline selenium concentrations were ≤1.15 μmol/L (P < 0.05).
  
  
  CONCLUSIONS
  These results indicate that GPx1 Pro200Leu variants do not substantially modify the response of whole-blood GPx to selenium supplementation in individuals with relatively high plasma selenium concentrations. A nutrient-gene interaction was observed when the baseline selenium concentration was low, but this requires independent confirmation. This trial was registered at www.actr.org.au as ACTRN12605000412639 and ACTRN12606000197538.
authors.affiliation: Departments of Human Nutrition, University of Otago, Dunedin, New Zealand. jody.miller@otago.ac.nz
authors.forename: Jody C
authors.initials: JC
authors.lastname: Miller
authors.forename: Christine D
authors.initials: CD
authors.lastname: Thomson
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Williams
authors.forename: Nathalie
authors.initials: N
authors.lastname: van Havre
authors.forename: Gerard T
authors.initials: GT
authors.lastname: Wilkins
authors.forename: Ian M
authors.initials: IM
authors.lastname: Morison
authors.forename: Jackie L
authors.initials: JL
authors.lastname: Ludgate
authors.forename: C Murray
authors.initials: CM
authors.lastname: Skeaff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D003324:Coronary Artery Disease / Q000097:blood* / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism; D019587:Dietary Supplements; D004311:Double-Blind Method; D004790:Enzyme Induction; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D005979:Glutathione Peroxidase / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000201:enzymology / Q000378:metabolism; D008875:Middle Aged; D009520:New Zealand; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D012643:Selenium / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D012645:Selenomethionine / Q000008:administration & dosage; D000094765:Glutathione Peroxidase GPX1
chemical_list: D012645:Selenomethionine; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human