title: Demethylation of the promoter region of GPX3 in a newborn with classical phenylketonuria.
abstract: OBJECTIVE
  Phenylketonuria (PKU) is characterized by a high phenylalanine (phe) in plasma and oxidative stress. However, the monitoring of oxidative stress in newborns with PKU using the activity levels of antioxidant enzymes is not optimal. We investigated the possibility of monitoring an increased reactive oxygen species (ROS) production using DNA methylation changes of an oxidative stress response element in the promoter region of an enzymatic antioxidant gene.
  
  
  METHODS
  Using DNA extracted from blood leukocytes, the cytosine phosphodiester bond guanine positions of an overlapping CCAAT box/metal response element (CGATTGGCTG) of the glutathione peroxidase 3 promoter activated by oxidative stimuli and expressed in plasma were analysed for methylation changes in 20 newborns with hyperphenylalaninemia and 20 healthy controls.
  
  
  RESULTS
  A demethylated allele was detected in a PKU patient at a phe level of 465μmol/L on day 2 after birth, but not in other patients (phe<465μmol/L, ≥day 2 after birth; phe>465μmol/L, ≥day 3 after birth) and healthy controls (phe<465μmol/L, ≥day 2 after birth).
  
  
  CONCLUSIONS
  The detection of the demethylated allele could be time and phe concentration dependent. The demethylated allele is suggested as an early epigenetic marker for an extracellular monitoring of an increased ROS production in newborns with PKU.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel, 18-20 Vienna, Austria. Electronic address: bellarmine.item@meduniwien.ac.at.
authors.forename: Chike Bellarmine
authors.initials: CB
authors.lastname: Item
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel, 18-20 Vienna, Austria.
authors.forename: Sharmane
authors.initials: S
authors.lastname: Escueta
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel, 18-20 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schanzer
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel, 18-20 Vienna, Austria.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Farhadi
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel, 18-20 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Metz
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel, 18-20 Vienna, Austria.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zeyda
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel, 18-20 Vienna, Austria.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Möslinger
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel, 18-20 Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Greber-Platzer
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel, 18-20 Vienna, Austria.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Konstantopoulou
mesh_terms: D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010661:Phenylketonurias / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: C486484:GPX3 protein, human; D005979:Glutathione Peroxidase
keywords: Demethylation; Glutathione peroxidase 3; Hyperphenylalaninemia; Newborn; Oxidative stress