Association between single nucleotide polymorphisms in non-coding regions of the insulin (INS) gene and schizophrenia

Schizophrenia is a psychotic disorder with high heritability. There are also indications that impaired cellular signalling via the insulin receptor-A and the insulin-like growth factor 1 receptor may play a role in its pathogenesis. Insulin, and possibly also C-peptide, are ligands to these receptors. The insulin gene, coding both insulin and C-peptide, has however not been genetically studied in schizophrenia. Therefore, this study was undertaken to investigate the involvement of this gene in schizophrenia susceptibility.

For identification of single nucleotide polymorphisms (SNPs) of interest, the whole insulin gene and parts of its promoter region were first DNA sequenced in two subgroups of the study population (37 schizophrenia patients with heredity for schizophrenia or related psychosis, and 25 controls), and mapped to the reference sequence. Then, 7 identified SNPs of potential interest were typed by TaqMan® SNP Genotyping Assays in the whole study population, consisting of 94 patients with schizophrenia and 60 controls.

Allele frequencies tended to differ between patients and controls for two of the 7 SNPs, rs5505 and rs3842749 (p=0.077 and p=0.078, respectively), whereas subgroup analyses of diabetes mellitus (type 1 or 2) and/ or heredity for diabetes mellitus (type 1 or 2) in patients and controls showed overall significant differences in genotype/ allele frequencies solely for rs5505 (p=0.021/ 0.023).

These findings are of interest, as the two SNPs - rs5505 and rs3842749 - may have regulatory function on the coding of insulin and C-peptide, against which increased antibody reactivity has been previously reported in schizophrenia.