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mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain1.76 MB
Published VersionCC BY V4.0, Open Access
Journal article
mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain
Genes, Vol.8(1), pp.1-11
2017
PMCID: PMC5295009
PMID: 28054990
Abstract
Serotonin receptor 2A (HTR2A) is an important signalling factor implicated in cognitive functions and known to be associated with schizophrenia. The biological significance of HTR2A in schizophrenia remains unclear as molecular analyses including genetic association, mRNA expression and methylation studies have reported inconsistent results. In this study, we examine HTR2A expression and methylation and the interaction with HTR2A polymorphisms to identify their biological significance in schizophrenia. Subjects included 25 schizophrenia and 25 control post-mortem brain samples. Genotype and mRNA data was generated by transcriptome sequencing. DNA methylation profiles were generated for CpG sites within promoter-exon I region. Expression, genotype and methylation data were examined for association with schizophrenia. HTR2A mRNA levels were reduced by 14% (p = 0.006) in schizophrenia compared to controls. Three CpG sites were hypermethylated in schizophrenia (cg5 p = 0.028, cg7 p = 0.021, cg10 p = 0.017) and HTR2A polymorphisms rs6314 (p = 0.008) and rs6313 (p = 0.026) showed genetic association with schizophrenia. Differential DNA methylation was associated with rs6314 and rs6313. There was a strong correlation between HTR2A DNA methylation and mRNA expression. The results were nominally significant but did not survive the rigorous Benjamini-Hochberg correction for multiple testing. Differential HTR2A expression in schizophrenia in our study may be the result of the combined effect of multiple differentially methylated CpG sites. Epigenetic HTR2A regulation may alter brain function, which contributes to the development of schizophrenia.
Details
- Title
- mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain
- Authors
- Sern-Yih Cheah (Author) - Queensland University of TechnologyBruce R Lawford (Author) - Queensland University of TechnologyRoss Young (Author) - Queensland University of TechnologyCharles P Morris (Author) - Queensland University of TechnologyJoanne Voisey (Author) - Queensland University of Technology
- Publication details
- Genes, Vol.8(1), pp.1-11
- Publisher
- MDPI AG
- Date published
- 2017
- DOI
- 10.3390/genes8010014
- ISSN
- 2073-4425
- PMID
- 28054990; PMC5295009
- Copyright note
- Copyright (c) 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
- Organisation Unit
- University of the Sunshine Coast, Queensland; Office of the Deputy Vice-Chancellor (Research and Innovation)
- Language
- English
- Record Identifier
- 99551705202621
- Output Type
- Journal article
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- Genetics & Heredity
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