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Genes 2017, 8(1), 14; doi:10.3390/genes8010014

mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain

1
School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia
2
Discipline of Psychiatry, Royal Brisbane and Women’s Hospital, Herston, Queensland 4006, Australia
3
Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Dennis R. Grayson
Received: 20 September 2016 / Revised: 21 December 2016 / Accepted: 22 December 2016 / Published: 4 January 2017
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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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. View Full-Text
Keywords: HTR2A; schizophrenia association; mRNA expression; DNA methylation; rs6314; rs6313; epigenetics HTR2A; schizophrenia association; mRNA expression; DNA methylation; rs6314; rs6313; epigenetics
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MDPI and ACS Style

Cheah, S.-Y.; Lawford, B.R.; Young, R.M.; Morris, C.P.; Voisey, J. mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain. Genes 2017, 8, 14.

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