Epigenetics of schizophrenia: A focus on the DNA methylation mechanism and expression of DISC1 gene

• Main Authors: A.Talib, Norlelawati, Ku Zaifah, Norsidah, Abdullah, Kartini, Abd. Rahim, Nour El Huda
• Format: Monograph
• Language: English
• Published: 2018
• Subjects: RM Therapeutics. Pharmacology; RZ400 Mental healing
• Online Access: http://irep.iium.edu.my/63787/1/PROJECT%20REPORT%20PROFILE.pdf; http://irep.iium.edu.my/63787/
• Institution: Universiti Islam Antarabangsa Malaysia

Epigenetic DNA methylation and Schizophrenia The evidence of Disrupted in Schizophrenia 1 (DISC1) gene role in schizophrenia came through functional and animal studies. However the exact genetic basis is yet established. As meta-analyses findings have denied DISC1 variants as the genetic basis, emphasis is now shifted to genetic defect such as copy number and epigenetic which have not been well explored. The project explored the epigenetic regulation of DISC1 gene and other neurodevelopmental and neurotransmitter genes that were strongly advocated as candidate genes of schizophrenia. A comparative cross sectional study consisted of 110 schizophrenia and 122 healthy control were recruited. Method for DNA methylation quantitation using high resolution melting (HRM) and MethylLight assays were established and used to quantify the methylation percentage. The optimized HRM assay for DISC1clearly demonstrated the serial methylated percentage differentiation of 0%, 25%, 50%, 75% and 100% accordingly. However, we found DISC1 methylation has no relationship with schizophrenia (p >0.05). With similar approach, COMT and RELN DNA methylation were investigated. We found, a significantly higher level of methylation of the RELN and COMT promoter in patients with schizophrenia compared to controls (p=0.005) and reduced RELN but not COMT expression in the methylated group as compared to the non-methylated group. The findings suggest possibility of DNA methylation of RELN and COMT gene effects in the pathogenesis of schizophrenia.