title: The insulin receptor substrate-4 (IRS-4) gene and schizophrenia: no evidence for a main genetic factor, however one report of a single schizophrenia patient with a mutation.
abstract: OBJECTIVE
  Since there are clear indications that schizophrenia is a systemic disorder, we sought for a common molecular basis for schizophrenia abnormalities in brain and body. Our hypothesis was that an impaired insulin/ insulin-like growth factor signalling in cells might underlie both structural and functional brain changes and peripheral abnormalities in schizophrenia. No associations between polymorphisms in the genes for insulin-like growth factor 1 or its receptor and schizophrenia have been reported. However, the insulin receptor substrates 1-4 linking both the insulin and insulin-like growth factor 1 receptors with intracellular pathways have not been extensively studied in schizophrenia. In this study, we therefore chose to study the insulin receptor substrate-4 (IRS-4) gene as a candidate gene in schizophrenia.
  
  
  METHODS
  The IRS-4 gene of 93 patients and 59 control subjects was screened for DNA sequence variations, followed by case-control analyses of 10 detected single nucleotide polymorphisms.
  
  
  RESULTS
  No significant genotype, allele or haplotype associations were found with the schizophrenia illness. However, one female patient with paranoid schizophrenia had an IRS-4 gene mutation at position 107863596, resulting in a change in amino acid coding from histidine to tyrosine at position 879.
  
  
  CONCLUSIONS
  Although this study supports the view that the IRS-4 gene is not of major importance for the aetiology of the vast majority of schizophrenia cases, our finding of this single patient with schizophrenia and a mutation in the IRS-4 gene may point to that the insulin/ insulin-like growth factor signalling system in cells is still of interest in the future search for schizophrenia genes.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden. Kristina.Melkersson@ki.se
authors.forename: Kristina
authors.initials: K
authors.lastname: Melkersson
authors.forename: Bengt
authors.initials: B
authors.lastname: Persson
authors.forename: Thorbjörn
authors.initials: T
authors.lastname: Hongslo
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
chemical_list: C107686:IRS4 protein, human; D055504:Insulin Receptor Substrate Proteins