Association study of GSK3 gene polymorphisms with schizophrenia and clozapine response

Rationale: A number of human and animal studies implicate GSK3 in the pathophysiology and genetics of schizophrenia. In general, the data suggest that phosphorylation levels of GSK3β are reduced in schizophrenia, resulting in increased GSK3β activity. Since GSK3β regulation is altered in schizophrenia, polymorphic variation in this gene may affect susceptibility to schizophrenia or treatment response. Objective: To analyze GSK3β genetic variants for association with schizophrenia and clozapine response. Materials and methods: We examined GSK3β markers in 185 matched case-control subjects, 85 small nuclear families, and 150 schizophrenia patients treated with clozapine for 6 months. Results: Three markers (rs7624540, rs4072520, and rs6779828) showed genotypic association with schizophrenia in the case-control sample. We did not observe any family and clozapine response association with a specific allele, genotype, or haplotype. Conclusions: Our results suggest that GSK3β polymorphisms might be involved in schizophrenia risk but do not appear to play a significant role in clozapine response.