The type 2 diabetes mellitus susceptibility gene IGF2BP2 is associated with schizophrenia in a Han Chinese Population

BACKGROUND: Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus, and type 2 diabetes mellitus has shown an association with the rs4402960 gene polymorphism in the insulin-like growth factor II messenger RNA (mRNA)-binding protein 2 gene (IGF2BP2). We tested this polymorphism and mRNA expression levels of IGF2BP2 for an association in Han Chinese patients with schizophrenia compared to healthy controls. METHOD: The rs4402960 polymorphism was genotyped in 790 chronic schizophrenic patients (diagnosed according to DSM-IV) and 1,083 unrelated healthy controls in a case-control design. The IGF2BP2 gene expression levels were assayed in 34 patients with chronic schizophrenia and 30 healthy controls by using real-time polymerase chain reaction (PCR). The study was conducted between 2005 and 2007. RESULTS: We found significant differences in the rs4402960 genotype (χ(2)2 = 7.316, P = .026) and allele (χ(2)1 = 7.056, P = .008) distributions between the patient and control groups. The rs4402960 T allelic frequency was significantly higher in male schizophrenic patients than male controls (28.9% vs 23.5%; P = .004) but not in female patients compared to female controls (27.1% vs 25.5%; P = .498). When real-time PCR was used, the IGF2BP2 gene's isoform B expression levels were significantly greater in schizophrenia than controls (P = .0008). CONCLUSIONS: These results suggest that the IGF2BP2 gene may play a role in susceptibility to schizophrenia, supporting the hypothesis that the co-occurrence of type 2 diabetes mellitus and schizophrenia may be explained by shared genetic risk variants. However, this finding remains preliminary since this association has yet to be replicated.