Screening for mutations in the GBA1 and LRRK2 genes in schizophrenia in the Northwestern region of Russia

Schizophrenia (SCZ) is a severe mental disorder which exact pathogenesis remains unknown. The disorder has been linked to disturbances in lipid metabolism and lysosomal function. A link between this disorder and Parkinson's disease (PD) is suggested. Pathogenic mutations in the GBA1 gene, which lead to dysfunction of the lysosomal enzyme glucocerebrosidase, are a highrisk factor of PD. Meanwhile, mutations in the LRRK2 gene are the most common cause of hereditary forms of PD and may indirectly affect the activity of this enzyme. GBA1and LRRK2related PD are the most prevalent forms of the disease known today. Materials and Methods: In this study, we used PCR-RFLP and real-time PCR allelic discrimination to assess the frequency of mutations in the LRRK2 (G2019S) and GBA1 (N370S, L444P, E326K) genes among 161 SCZ patients and 434 control individuals residing in the Northwestern region of Russia. Results: The study found no association between the investigated mutations and the risk of SCZ. Among SCZ patients, no carriers of the N370S mutation in the GBA1 gene or the G2019S mutation in the LRRK2 gene were identified. The frequency of GBA1 mutations (L444P+N370S+E326K) among SCZ patients was found to be 3.2%. Conclusions: Thus, this study demonstrated that mutations in the GBA1 gene are not associated with the risk of SCZ.