title: Association of an UCP4 (SLC25A27) haplotype with ultra-resistant schizophrenia.
abstract: OBJECTIVE
  Neuronal uncoupling proteins are involved in the regulation of reactive oxygen species production and intracellular calcium homeostasis, and thus, play a neuroprotective role. In order to explore the potential consequences of neuronal uncoupling proteins variants we examined their association in a sample of Caucasian patients suffering from schizophrenia and phenotyped them according to antipsychotic response.
  
  
  METHODS
  Using a case-control design, we compared the frequencies of 15 genetic variants spanning UCP2, UCP4 and UCP5 in 106 French Caucasian patients suffering from schizophrenia and 127 healthy controls. In addition, patients with schizophrenia who responded to antipsychotic treatment were compared with patients with ultra-resistant schizophrenia (URS). This latter population presented no clinical, social and/or occupational remission despite at least two periods of treatment with conventional or atypical antipsychotic drugs and also with clozapine.
  
  
  RESULTS
  There were no differences in the distribution of the respective alleles between URS and responding patients. However, one haplotype spanning UCP4 was found to be significantly under-represented in URS patients. This relationship remained significant after multiple testing corrections.
  
  
  CONCLUSIONS
  Although our sample is of limited size and not representative of schizophrenia as a whole, the association found between the URS group and the UCP4 haplotype is noteworthy as it may influence treatment outcome in schizophrenia.
authors.affiliation: INSERM, Laboratoire de Physiopathologie des Maladies Psychiatriques, U894 Centre de Psychiatrie et Neurosciences, Paris, France.
authors.forename: Fayçal
authors.initials: F
authors.lastname: Mouaffak
authors.forename: Oussama
authors.initials: O
authors.lastname: Kebir
authors.forename: Alfredo
authors.initials: A
authors.lastname: Bellon
authors.forename: Raphael
authors.initials: R
authors.lastname: Gourevitch
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tordjman
authors.forename: Annie
authors.initials: A
authors.lastname: Viala
authors.forename: Bruno
authors.initials: B
authors.lastname: Millet
authors.forename: Nematollah
authors.initials: N
authors.lastname: Jaafari
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Olié
authors.forename: Marie Odile
authors.initials: MO
authors.lastname: Krebs
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005602:France; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D000071246:Uncoupling Protein 2; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; C116584:SLC25A14 protein, human; C117577:SLC25A27 protein, human; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2