title: Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria.
abstract: BACKGROUND
  Several studies have highlighted disturbance of redox homeostasis in patients with phenylketonuria (PKU) which may be associated with neurological disorders observed in patients, especially during adulthood when phenylalanine restrictive diets are not maintained. The aim of this study was to assess the antioxidant profile in a cohort of PKU patients in comparison to the controls and to evaluate its relation to biochemical parameters especially phenylalaninemia.
  
  
  METHODS
  We measured RNA expression of 22 antioxidant genes and reactive oxygen species (ROS) levels in white blood cells of 10 PKU patients and 10 age- and gender-matched controls. We also assessed plasma amino acids, vitamins, oligo-elements, and urinary organic acids concentrations. Then we evaluated the relationship between redox status and biochemical parameters.
  
  
  RESULTS
  In addition to expected biochemical disturbances, we highlighted a significant global decrease of antioxidant genes expression in PKU patients in comparison to the controls. This global decrease of antioxidant genes expression, including various isoforms of peroxiredoxins, glutaredoxins, glutathione peroxidases, and superoxide dismutases, was significantly correlated to hyperphenylalaninemia.
  
  
  CONCLUSIONS
  This study is the first to evaluate the expression of 22 antioxidant genes in white blood cells regarding biochemical parameters in PKU. These findings highlight the association of hyperphenylalaninemia with antioxidant genes expression. New experiments to specify the role of oxidative stress in PKU pathogenesis may be useful in suggesting new recommendations in PKU management and new therapeutic trials based on antioxidant defenses.
authors.affiliation: Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France. charlotte.veyrat@live.fr.|INSERM U930, Université François Rabelais Tours, Tours, France. charlotte.veyrat@live.fr.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.affiliation: CNRS UMR 7292 - équipe LNOx, Université François Rabelais Tours, Tours, France.|Service d'hématologie biologique, CHRU de Tours, Tours, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Debeissat
authors.affiliation: Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France.|INSERM U930, Université François Rabelais Tours, Tours, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.affiliation: Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France.|INSERM U930, Université François Rabelais Tours, Tours, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Patin
authors.affiliation: Service de médecine interne, CHRU de Tours, Tours, France.|INSERM U1069, Université François Rabelais Tours, Tours, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Henique
authors.affiliation: INSERM U930, Université François Rabelais Tours, Tours, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
authors.affiliation: Laboratoire de biochimie et biologie moléculaire, hôpital Bretonneau CHRU de Tours, Tours, France.|INSERM U930, Université François Rabelais Tours, Tours, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Antar
authors.affiliation: INSERM CIC 1415, CHRU de Tours, Tours, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gissot
authors.affiliation: CNRS UMR 7292 - équipe LNOx, Université François Rabelais Tours, Tours, France.|Service d'hématologie biologique, CHRU de Tours, Tours, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Herault
authors.affiliation: Service de médecine interne, CHRU de Tours, Tours, France.|INSERM U1069, Université François Rabelais Tours, Tours, France.
authors.forename: François
authors.initials: F
authors.lastname: Maillot
keywords: PKU; Phenylketonuria; RNA antioxidant profile; Redox status