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Evidence for a negative association between schizophrenia and a polymorphism in the insulin receptor substrate-3 (IRS-3) gene
Karolinska Institute, Sweden .
Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
2012 (English)In: Neuro - endocrinology letters, ISSN 0172-780X, Vol. 33, no 3, 321-330 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: 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 and insulin-like growth factor signalling in cells might underlie changes in both brain and body in schizophrenia. In this regard, the insulin receptor substrates 1-4, linking both the insulin and insulin-like growth factor-1 receptors with intracellular pathways, might be of interest to study genetically. In the present study, we chose to study the insulin receptor substrate-3 (IRS-3) gene as a candidate gene in schizophrenia. less thanbrgreater than less thanbrgreater thanMETHODS: The IRS-3 gene of 93 patients with the diagnosis of schizophrenia according to DSM-IV criteria and 57 healthy control subjects was screened for DNA sequence variations, followed by case-control analyses of total 10 detected polymorphisms. less thanbrgreater than less thanbrgreater thanRESULTS: The A/G genotype of the single nucleotide polymorphism (SNP) rs117078492 in the IRS-3 gene occurred in 5.3% of the control subjects compared with in 0% of the patients (p=0.05). Similarly, the haplotypes 5 and 3X, constructed from polymorphisms in the IRS-3 gene and including the A allele of this A/G SNP, occurred only in the control subjects and not in the patients (5.3% vs 0%, p=0.05). less thanbrgreater than less thanbrgreater thanCONCLUSION: Our findings suggest that individuals carrying the A allele of this A/G SNP in the IRS-3 gene as well as the estimated haplotypes 5 or 3X including this A allele, have a protection against schizophrenia development.

Place, publisher, year, edition, pages
Brain Research Promotion , 2012. Vol. 33, no 3, 321-330 p.
Keyword [en]
case-control study, DNA sequencing, height, IRS-3, IRS-3P, psychotic disorder, schizophrenia, single nucleotide polymorphism
National Category
Engineering and Technology
URN: urn:nbn:se:liu:diva-79114DOI: 10.1016/S0924-9338(13)77131-1ISI: 000305102500019OAI: diva2:538239

Funding Agencies|Swedish Research Council||Swedish Society of Medicine||

Available from: 2012-06-29 Created: 2012-06-29 Last updated: 2014-10-30

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ReferencesLink to record
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