title: A possible association between an insertion/deletion polymorphism of the NQO2 gene and schizophrenia.
abstract: OBJECTIVE
  Glutathione-S-transferases, NAD(P)H: quinone oxidoreductase1 (NQO1) and NRH: quinone oxidoreductase2 (NQO2) provide important cellular defences against the neurotoxicity induced by catecholamine-derived o-quinones and oxidative stress during redox cycling. In this study, we investigated the association between polymorphisms of the NQO2 gene and schizophrenia.
  
  
  METHODS
  We analysed the promoter and coding regions of the NQO2 gene for 102 patients with schizophrenia and for 234 controls using single-strand conformational change polymorphism and PCR direct-sequencing analyses and the RNA concentration of NQO2 in white blood cells isolated from peripheral blood was measured.
  
  
  RESULTS
  We identified 12 variants including the insertion/deletion (I/D) polymorphism of the 29 base pair nucleotide sequence in the promoter region. The frequency of the D allele was significantly higher in the schizophrenic group than in the control group (P=0.0109). Especially, in patients with the episodic type as course specifiers, this value was highly significant (P=0.0016) and the significance remained after the Bonferroni correction. The 29 base pair nucleotide sequence contains four repeats of the putative core sequence of the Sp1-binding cis-element that is important in the activation of gene expression. Our preliminary data, although sample size was not enough, demonstrated that the RNA concentration of NQO2 in white blood cells isolated from peripheral blood was higher in individuals homozygous (II) for the I allele than in those heterozygous (ID) or homozygous (DD) for the D allele.
  
  
  CONCLUSIONS
  The present data suggest that individuals with the deletion of the 29 base pair sequence in the promoter region of the NQO2 gene may confer susceptibility to a certain form of schizophrenia.
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Tokyo, Shinjuku-ku, Japan. sjharada@srl.stl.inc.co.jp
authors.forename: Shoji
authors.initials: S
authors.lastname: Harada
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tachikawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawanishi
mesh_terms: D000328:Adult; D001483:Base Sequence; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011808:Quinone Reductases / Q000235:genetics*; D012559:Schizophrenia / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases