Influence of CTNNB1 rs2953 polymorphism on schizophrenia susceptibility in Chinese Han population through modifying miR-485 binding to CTNNB1.

Abstract

Schizophrenia (SCZ) and bipolar disorder (BD) are two major neuropsychiatric diseases that are the most substantial causes of disability and mortality worldwide. CTNNB1 encodes beta-catenin, an important protein in canonical Wnt signaling. We aimed to investigate the association between the rs2953 of CTNNB1 and the risk of SCZ and BD and to further explore the function of rs2953. A total of 1658 samples (548 SCZ cases, 512 BD cases, and 598 controls) were examined in terms of the genotype of CTNNB1 rs2953. The mRNA expression level of CTNNB1 significantly increased in the SCZ and BD groups compared with that in the control group. Significant association remained between CTNNB1 3'-untranslated region (UTR) variant rs2953 and SCZ susceptibility (additive and dominant model) after gender and age were adjusted. rs2953 disrupted the binding of CTNNB1 and miR-485. miR-485 significantly suppressed the luciferase activity of CTNNB1-T vector by binding to the CTNNB1 3'-UTR containing the T allele of rs2953. The mRNA expression of CTNNB1 can be used as a biomarker for the diagnosis of SCZ and BD. The 3'-UTR variant rs2953 in CTNNB1 influences the risk of SCZ in the Han Chinese population and modifies the binding of miR-485 to CTNNB1.