DNA methylation of reelin (RELN) gene in schizophrenia

Abstract

Schizophrenia is a complex psychiatric disorder that affects 1% of global population worldwide. Epigenetics studies have speculated that the expressions of several implicated genes of schizophrenia are altered by environmental factors through DNA methylation. Reelin (RELN), a gene required for brain development, is implicated in the pathogenesis of schizophrenia. Study so far on the methylation status of RELN is insufficient to affirm the role of RELN DNA methylation in schizophrenia. The study aimed to investigate the role of RELN methylation in schizophrenia. A total of 110 schizophrenia patients from Hospital Tengku Ampuan Afzan, Pahang and healthy controls were recruited. Data collected include demographic profile, clinical data, and psychopathological symptoms that were assessed through Positive and Negative Syndrome Scale (PANSS). DNA methylation of RELN was analysed using MethyLight TaqMan® assays. The study found significantly higher RELN methylation level in schizophrenia as compared to healthy controls (p = 0.004). However, there was no significant correlation of RELN methylation percentage with psychological symptoms in schizophrenia. The RELN mRNA expression of samples with high methylation is significantly depressed (25 folds) relative to low methylation samples. In conclusion, the RELN DNA methylation differences and its relationship with downregulation of its mRNA expression suggest RELN epigenetic roles in pathophysiology of schizophrenia.