title: No association between glutathione-synthesis-related genes and Japanese schizophrenia.
abstract: OBJECTIVE
  Schizophrenia is a major psychiatric disorder with complex genetic, environmental, and psychological causes, and oxidative stress may be involved in the pathogenesis of the disease. Glutathione (GSH), one of the main cellular non-protein antioxidants and redox regulators, and altered GSH levels have been reported in various regions in patients with schizophrenia. Three enzymes are responsible for GSH synthesis: glutamate cysteine ligase modifier (GCLM), glutamate cysteine ligase catalytic subunit (GCLC), and glutathione synthetase (GSS). Previously, positive associations between GCLM and schizophrenia were reported in Europeans, but not in the Japanese population. Thus, in this study, we investigated the association between the GSH synthesis genes (GCLM, GCLC, and GSS) and schizophrenia in Japanese individuals.
  
  
  METHODS
  Seventeen single-nucleotide polymorphisms (SNP) in GCLM, GCLC, and GSS were genotyped in 358 patients with schizophrenia and in 359 controls.
  
  
  RESULTS
  No SNP showed a significant association between their allelic or genotypic frequencies and schizophrenia. Case-control haplotype association analysis using windows of two or three SNP showed no significant associations with schizophrenia. The case-control haplotype analyses based on the ascertained linkage disequilibrium blocks also showed no significant associations in any genes with schizophrenia.
  
  
  CONCLUSIONS
  The three primary GSH synthesis genes do not have an apparent degree of association with schizophrenia in the Japanese population.
authors.affiliation: Juntendo University Schizophrenia Projects, Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hanzawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohnuma
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Nagai
authors.forename: Nobuto
authors.initials: N
authors.lastname: Shibata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Maeshima
authors.forename: Hajime
authors.initials: H
authors.lastname: Baba
authors.forename: Tokiko
authors.initials: T
authors.lastname: Hatano
authors.forename: Yuto
authors.initials: Y
authors.lastname: Takebayashi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Hotta
authors.forename: Maiko
authors.initials: M
authors.lastname: Kitazawa
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D005981:Glutathione Synthase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*
chemical_list: C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase