Evidence for a negative association between schizophrenia and a polymorphism in the insulin receptor substrate-3 (IRS-3) gene.

Melkersson K, Persson B

Neuro Endocrinol. Lett. 33 (3) 321-330 [2012-05-29; online 2012-05-29]

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. 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. 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). 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.

NGI Uppsala (Uppsala Genome Center)

National Genomics Infrastructure

PubMed 22635093

DOI 10.1016/S0924-9338(13)77131-1

Crossref 10.1016/S0924-9338(13)77131-1

pii: NEL330312A01