Association Between Gene Polymorphisms of RSPO2 of the Wnt Signaling Pathway and Schizophrenia in the Korean Population

Objective The study aimed to investigate whether RSPO2 gene polymorphisms are associated with schizophrenia susceptibility, focusing on five specific single nucleotide polymorphisms (SNPs). Additionally, the study evaluated the expression of Rspo2 in a schizophrenic-like mouse model and examined its relationship with clinical symptoms. Methods The study included 159 schizophrenia patients and 448 controls. Clinical symptoms were assessed using the Operational Criteria Checklist for Psychotic Illness. Genotyping of five RSPO2 SNPs was performed to identify potential genetic associations with schizophrenia. Rspo2 mRNA expression levels were measured in the brains of MK-801-induced schizophrenic-like mice. Functional analysis of the rs374810 SNP was conducted using a luciferase assay to evaluate its effect on gene activity. Statistical analyses were used to compare genotype and allele frequencies and assess correlations with clinical outcomes. Results Significant associations were found between schizophrenia and two SNPs, rs374810 and rs423940. The A allele of rs374810 and the T allele of rs423940 were linked to an increased risk of schizophrenia (p=0.0049 and p=0.0044, respectively). Functional analysis revealed that the A allele of rs374810 significantly increased luciferase activity compared to the G allele, indicating a potential functional role. RSPO2 expression was also altered in the schizophrenic-like mouse model, suggesting its involvement in schizophrenia pathogenesis. Conclusion The findings indicate that RSPO2 gene polymorphisms, particularly rs374810 and rs423940, may contribute to schizophrenia susceptibility. Therefore, RSPO2 expression may be associated with the susceptibility to schizophrenia in the Korean population.