DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease

Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed on MD. Here we pe...

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Autores principales:	Marisa Flook, Alba Escalera-Balsera, Alvaro Gallego-Martinez, Juan Manuel Espinosa-Sanchez, Ismael Aran, Andres Soto-Varela, Jose Antonio Lopez-Escamez
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Meniere Disease cytokines WGBS hearing loss DNA methylation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/777206b1fe334c8e8ef0e718c699ba9f
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spelling	oai:doaj.org-article:777206b1fe334c8e8ef0e718c699ba9f2021-11-25T16:48:38ZDNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease10.3390/biomedicines91115302227-9059https://doaj.org/article/777206b1fe334c8e8ef0e718c699ba9f2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1530https://doaj.org/toc/2227-9059Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed on MD. Here we performed whole-genome bisulfite sequencing in 14 MD patients and six healthy controls, with the aim of identifying an MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (<i>n</i>= 9545), several of them in hearing loss genes, such as <i>PCDH15,</i> <i>ADGRV1</i> and <i>CDH23</i>. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including two UMR in an inter CpG island in the <i>PHB</i> gene. We suggest that the DNA methylation signature allows distinguishing between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.Marisa FlookAlba Escalera-BalseraAlvaro Gallego-MartinezJuan Manuel Espinosa-SanchezIsmael AranAndres Soto-VarelaJose Antonio Lopez-EscamezMDPI AGarticleMeniere DiseasecytokinesWGBShearing lossDNA methylationBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1530, p 1530 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Meniere Disease cytokines WGBS hearing loss DNA methylation Biology (General) QH301-705.5
spellingShingle	Meniere Disease cytokines WGBS hearing loss DNA methylation Biology (General) QH301-705.5 Marisa Flook Alba Escalera-Balsera Alvaro Gallego-Martinez Juan Manuel Espinosa-Sanchez Ismael Aran Andres Soto-Varela Jose Antonio Lopez-Escamez DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease
description	Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed on MD. Here we performed whole-genome bisulfite sequencing in 14 MD patients and six healthy controls, with the aim of identifying an MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (<i>n</i>= 9545), several of them in hearing loss genes, such as <i>PCDH15,</i> <i>ADGRV1</i> and <i>CDH23</i>. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including two UMR in an inter CpG island in the <i>PHB</i> gene. We suggest that the DNA methylation signature allows distinguishing between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.
format	article
author	Marisa Flook Alba Escalera-Balsera Alvaro Gallego-Martinez Juan Manuel Espinosa-Sanchez Ismael Aran Andres Soto-Varela Jose Antonio Lopez-Escamez
author_facet	Marisa Flook Alba Escalera-Balsera Alvaro Gallego-Martinez Juan Manuel Espinosa-Sanchez Ismael Aran Andres Soto-Varela Jose Antonio Lopez-Escamez
author_sort	Marisa Flook
title	DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease
title_short	DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease
title_full	DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease
title_fullStr	DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease
title_full_unstemmed	DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease
title_sort	dna methylation signature in mononuclear cells and proinflammatory cytokines may define molecular subtypes in sporadic meniere disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/777206b1fe334c8e8ef0e718c699ba9f
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DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease

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