Bioinformatic analysis on regulation of GGH gene in paranoid schizophrenia patients

The Gamma-Glutamyl Hydrolase (GGH) gene spans ۲۴ Kb on chromosome ۸q۱۲ in human and contain ۹exons. This gene produces γ-glutamyl hydrolase which is a lysomal enzyme involved in the metabolism offolates and anti-folates. An association between folate deficiency and schizophrenia has been reported. Inthis study, we analyzed the distinctive transcriptome alterations of GGH gene in paranoid schizophreniabioinformatically, which can uncover new genetic associations. The data related to this gene was obtainedfrom GEO datasets based on GSE۹۳۹۸۷ microarray gene expression study. The gene ontology and genomepathway analysis were performed by DAVID and KEGG databases respectively. The interaction amongproteins was constructed through STRING database. Based on DAVID disease-class, GGH gene is involvedin immune, neurological diseases. The volcano plot resulted from GEO analyses showed differentiallyexpression of GGH gene between paranoid schizophrenia samples and unaffected comparisons. The log۲foldchange was -۱.۸۸۷E-۱ for GGH gene that means its down-regulation in the patient samples. Thehypofunctional ۶۷۷C>T variant of the MTHFR gene has been associated with symptom risk in schizophrenia,as has Low serum folate levels. According to the STRING pathway, the MTHFR and GGH have correlationlink in metabolic pathway, carbon metabolism and one carbon pool by folate. The interactions of ۲۰ genesassociated with GGH retrieved from the GeneMania database and the network analysis showed their mostconnectivity in physical interactions. Our findings match with the evidence for ۵ genes (TRIP۶, GDI۱, OS-۹, PARK۷ and UGDH) related to schizophrenia disorder. It is concluded that the GGH gene and correlatedpathway can play important roles in human neurodegenerative diseases caused by certain abnormalities ofprotein synthesis, metabolic pathway, DNA synthesis, and gene expression.

کلیدواژه ها:

Gamma-Glutamyl Hydrolase ، Paranoid Disorder ، Folate Pathway