Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Marisa Flook
ORCID logo ,
Alba Escalera-Balsera
ORCID logo ,
Alvaro Gallego-Martinez
ORCID logo ,
Juan Manuel Espinosa-Sanchez
ORCID logo ,
Ismael Aran
,
Andres Soto-Varela
,
Jose Antonio Lopez-Escamez
*
Version 1 : Received: 28 September 2021 / Approved: 1 October 2021 / Online: 1 October 2021 (16:03:48 CEST)

A peer-reviewed article of this Preprint also exists.

Flook, M.; Escalera-Balsera, A.; Gallego-Martinez, A.; Espinosa-Sanchez, J.M.; Aran, I.; Soto-Varela, A.; Lopez-Escamez, J.A. DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease. Biomedicines 2021, 9, 1530. Flook, M.; Escalera-Balsera, A.; Gallego-Martinez, A.; Espinosa-Sanchez, J.M.; Aran, I.; Soto-Varela, A.; Lopez-Escamez, J.A. DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease. Biomedicines 2021, 9, 1530.

Abstract

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 in MD. Here we performed whole genome bisulfite sequencing in 14 MD patients and 6 healthy controls, with the aim of identifying a MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (N= 9,545), several of them in hearing loss genes such as PCDH15, ADGRV1 and CDH23. 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 2 UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows to distinguish between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.

Keywords

Meniere Disease; cytokines; WGBS; Hearing Loss; DNA methylation

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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