Associations between heredity, height, BMI, diabetes mellitus type 1 or 2 and gene variants in the insulin receptor (INSR) gene in patients with schizophrenia.

Objectives: Schizophrenia is a psychotic disorder with high heritability. There are also indications that an autoimmune-mediated process in the brain underlies development of schizophrenia, and that the insulin receptor A may constitute a main antigen target. Therefore, as the insulin receptor gene hitherto has been little studied in schizophrenia, this study was undertaken to investigate this gene in schizophrenia susceptibility.

Materials and methods: To identify gene variants of possible interest, the whole insulin receptor gene was first DNA-sequenced in all or subgroups of patients with schizophrenia and controls, using the Sanger method and the SOLiD technology. Then, association analyses of total 50 identified gene variants were carried out in the whole study population, consisting of 94 patients and 60 controls.

Results: No significant differences in genotype- and allele frequencies for the 50 gene variants were found between all patients and controls. However, in subgroup analyses, rs2229431 and rs747721248 tended to associate with heredity for schizophrenia, rs2229431 associated with height, rs41505247 with body mass index, rs59765738 and rs57476618 with diabetes mellitus (DM) type 1 and/ or heredity for DM type 1, and rs2962, rs2352954, rs2352955 and rs2252673 with DM type 2 and/ or heredity for DM type 2 in patients.

Conclusions: In this study, we show associations between heredity, height, body mass index, DM type 1, or DM type 2 and gene variants in the insulin receptor gene in patients with schizophrenia. Taken together, these findings clearly point to that the insulin receptor gene is involved in schizophrenia susceptibility.