DNA methylation analysis of AKT1 promoter and HTR2A Exon-I of Malaysian schizophrenia multiplex families with lower cognitive performance
Document Type
Article
Publication Date
3-1-2020
Abstract
Dysfunction of cognitive performance in schizophrenia has been associated with aberrant alteration of DNA methylation of several schizophrenia-risk genes. AKT1 and HTR2A are among the candidate genes for schizophrenia. Their expressions were found reduced in schizophrenia patients. Thus, we aimed to study the methylation status of AKT1 promoter and HTR2A exon-I in Malaysian schizophrenia patients and their affected family members. In this study, each participant was required to perform Trail Making Test (7117) part A and B to measure their cognitive performance. Genomic DNA extracted from the peripheral blood of 12 Malaysian schizophrenia families and 12 controls families, was subjected to bisulfite conversion. The methylation status of CpG sites of AKT1 promoter at Chr14: 104796054 and HTR2A exon-I at Chr13: 46896918 were identified using methylation-speafic polymerase chain reaction (MSP). Our results showed that schizophrenia patients performed worse in both TMT-A and B (p< 0.0001) than healthy controls. The patients also displayed significantly (p=0.023) high level of methylation in AKT1 promoter compared to controls. Meanwhile, no significant difference (p=0.248) in methylation status was observed in HTR2A exon-I between schizophrenia and control groups. Therefore, methylation of AKT1 promoter in peripheral bloods of patients may involve in cognitive impairment and schizophrenia pathology. In addition, we were able to demonstrate the heritability of DNA methylation status across family members.
Keywords
Cognitive performance, DNA methylation, Schizophrenia, Trail-Making Test
Divisions
fac_med
Funders
UTARRF [IPSR/RMC/UTARRF/2016-C1/T5],Malaysia Toray Science Foundation [4417/T04] [HIR/MOHE/MED/26]
Publication Title
Sains Malaysiana
Volume
49
Issue
3
Publisher
Penerbit Universiti Kebangsaan Malaysia
Publisher Location
FACULTY SCIENCE & TECHNOLOGY, BANGI, SELANGOR, 43600, MALAYSIA