1st International and 10th National Iranian Conference on Bioinformatics

Bioinformatic analysis on regulation of GGH gene in paranoid schizophrenia patients

Paper ID : 1185-ICB10

Authors:

Mehrnoosh Tavakoli, Mansoureh Azadeh *, پگاه جاوید

دپارتمان زیست فناوری نوین

Abstract:

The Gamma-Glutamyl Hydrolase (GGH) gene spans 24 Kb on chromosome 8q12 in human and contain 9 exons [1]. This gene produces γ-glutamyl hydrolase which is a lysomal enzyme involved in the metabolism of folates and anti-folates [2]. An association between folate deficiency and schizophrenia has been reported [3]. In this study, we analyzed the distinctive transcriptome alterations of GGH gene in paranoid schizophrenia bioinformatically, which can uncover new genetic associations. The data related to this gene was obtained from GEO datasets based on GSE93987 microarray gene expression study. The gene ontology and genome pathway analysis were performed by DAVID and KEGG databases respectively. The interaction among proteins was constructed through STRING database. Based on DAVID disease-class, GGH gene is involved in immune, neurological diseases. The volcano plot resulted from GEO analyses showed differentially expression of GGH gene between paranoid schizophrenia samples and unaffected comparisons. The log2fold change was -1.887E-1 for GGH gene that means its down-regulation in the patient samples. The hypofunctional 677C>T variant of the MTHFR gene has been associated with symptom risk in schizophrenia, as has Low serum folate levels [4]. According to the STRING pathway, the MTHFR and GGH have correlation link in metabolic pathway, carbon metabolism and one carbon pool by folate. The interactions of 20 genes associated with GGH retrieved from the GeneMania database and the network analysis showed their most connectivity in physical interactions. Our findings match with the evidence for 5 genes (TRIP6, GDI1, OS-9, PARK7 and UGDH) related to schizophrenia disorder. It is concluded that the GGH gene and correlated pathway can play important roles in human neurodegenerative diseases caused by certain abnormalities of protein synthesis, metabolic pathway, DNA synthesis, and gene expression.

Keywords:

Gamma-Glutamyl Hydrolase; Paranoid Disorder; Folate Pathway

Status : Paper Accepted (Poster Presentation)