Lack of association between sigma receptor gene variants and schizophrenia

Psychiatry Clin Neurosci. 2004 Aug;58(4):359-63. doi: 10.1111/j.1440-1819.2004.01268.x.


Several pharmacological studies suggest the possible involvement of sigma(1) receptors in the pathogenesis of schizophrenia. An association has been reported between schizophrenia and two variants (GC-241-240TT and Gln2Pro) in the sigma(1) receptor gene (SIGMAR1). We also previously reported that, along with T-485 A, these two variants alter SIGMAR1 function. To investigate the role of SIGMAR1 in conveying susceptibility to schizophrenia, we performed a case-control study. We initially screened for polymorphisms in the SIGMAR1 coding region using PCR-single strand conformation polymorphism analysis. The distribution of SIGMAR1 polymorphisms was analyzed in 100 schizophrenic and 104 control subjects. A novel G620A variant was detected in exon4. G620A was predicted to alter the amino acid represented by codon 211 from arginine to glutamine. Our case-control study showed no significant association between the T-485 A, GC-241-240TT, Gln2Pro, and G620A (Arg211Gln) variants and schizophrenia and clinical characteristics. These findings suggest that these SIGMAR1 variants may not affect susceptibility to schizophrenia.

MeSH terms

  • Adult
  • Amino Acid Substitution / genetics
  • Case-Control Studies
  • Codon / genetics
  • Exons / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation / genetics*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Receptors, sigma / genetics*
  • Schizophrenia / diagnosis
  • Schizophrenia / genetics*
  • Schizophrenic Psychology
  • Sigma-1 Receptor
  • Statistics as Topic


  • Codon
  • Receptors, sigma