DNA methylation analysis of AKT1 promoter and HTR2A Exon-I of Malaysian schizophrenia multiplex families with lower cognitive performance

Laere, Erna and Chow, Tze Jen and Tang, Pek Yee and Loh, Stew Yim and Yong, Hoi Sen and Kadir, Abdul and Bakar, Abu and Tee, Shiau Foon (2020) DNA methylation analysis of AKT1 promoter and HTR2A Exon-I of Malaysian schizophrenia multiplex families with lower cognitive performance. Sains Malaysiana, 49 (3). pp. 635-642. ISSN 0126-6039, DOI https://doi.org/10.17576/jsm-2020-4903-18.

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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.

Item Type: Article
Funders: UTARRF [IPSR/RMC/UTARRF/2016-C1/T5], Malaysia Toray Science Foundation [4417/T04] [HIR/MOHE/MED/26]
Uncontrolled Keywords: Cognitive performance; DNA methylation; Schizophrenia; Trail-Making Test
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 05 Oct 2023 03:19
Last Modified: 05 Oct 2023 03:19
URI: http://eprints.um.edu.my/id/eprint/36847

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