title: Glutamate cysteine ligase (GCL) and self reported depression: an association study from the HUNT.
abstract: BACKGROUND
  There is increasing evidence suggesting oxidative stress may play a role in the aetiology of depression. Glutathione is the brain's predominant free radical scavenger, and associated polymorphisms of the glutamate cysteine ligase (GCL) gene have been reported for related psychiatric disorders. The aim of the study was to investigate candidate polymorphisms of GCL validated in schizophrenia and their association with current state depression, as measured by the Hospital Anxiety and Depression Scale (HADS).
  
  
  METHODS
  Polymorphisms were genotyped on 983 cases and 967 controls selected from a population sample of adults participating in the Nord-Trøndelag Health Study. Cases were the top scoring individuals (98.5th percentile) on the HADS depression subscale while the controls were randomly selected from below this cut-off. The polymorphisms comprised three SNPs from GCLM, the gene encoding the GCL modifier and 9 SNPs plus a trinucleotide repeat (TNTR) from intron 1 and the 5'UTR of GCLC, the gene encoding the GCL catalytic subunit. Using the linkage disequilibrium between the GCLC markers we also tested whether SNPs could represent the variation of the TNTR.
  
  
  RESULTS
  The candidate polymorphisms showed no evidence for association with depression. The C allele of SNP rs9474592 is coupled with the 9 GAG repeats allele of the TNTR, r²=0.81. None of the other SNPs either individually or as two or three-SNP haplotypes was associated with the TNTR alleles.
  
  
  CONCLUSIONS
  Depression was self-reported and measured at one time point.
  
  
  CONCLUSIONS
  This study provides no evidence to suggest that polymorphisms of GCL are associated with self-reported depression.
authors.affiliation: School of Medicine, Deakin University, Geelong, Australia. mikebe@barwonhealth.org.au
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Stefan
authors.initials: S
authors.lastname: Johansson
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
authors.forename: Lana
authors.initials: L
authors.lastname: Williams
authors.forename: Craig
authors.initials: C
authors.lastname: Olsson
authors.forename: Jan
authors.initials: J
authors.lastname: Haavik
authors.forename: Ottar
authors.initials: O
authors.lastname: Bjerkeset
mesh_terms: D000483:Alleles; D003863:Depression / Q000201:enzymology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D006801:Humans; D008297:Male; D009664:Norway; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales
chemical_list: D005721:Glutamate-Cysteine Ligase