Original Research April 15, 2013

The Type 2 Diabetes Mellitus Susceptibility Gene IGF2BP2 Is Associated With Schizophrenia in a Han Chinese Population

Xuan Zhang, PhD; Li Hui, PhD; Yang Liu, PhD; Zhen-Qi Wang, PhD; Yang You, MD; Li-ning Miao, MD, PhD; Shi-Long Sun, PhD; Song-Lei Guan, PhD; Yutao Xiang, MD, PhD; Thomas R. Kosten, MD; Xiang Yang Zhang, MD, PhD

J Clin Psychiatry 2013;74(4):e287-e292

Article Abstract

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 (χ22 = 7.316, P = .026) and allele (χ21 = 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.

J Clin Psychiatry 2013;74(4):e287-e292

Submitted: April 11, 2012; accepted October 25, 2012(doi:10.4088/JCP.12m07846).

Corresponding author: Xiang Yang Zhang, MD, PhD, Jilin University, 18 Ziqiang St, Changchun 130041, China ([email protected]).

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