@misc{10481/71234,
year = {2021},
url = {http://hdl.handle.net/10481/71234},
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
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 (n= 9545), 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 two
UMR in an inter CpG island in the PHB 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.},
organization = {PI17/1644 grant from ISCIII by FEDER Funds from the EU},
organization = {F18/00228 grant from ISCIII by FEDER Funds from the EU},
organization = {AEB is funded by the
EU’s Horizon 2020 Research and Innovation Programme, Grant Agreement Number 848261.},
publisher = {MDPI},
keywords = {Meniere Disease},
keywords = {Cytokines},
keywords = {WGBS},
keywords = {Hearing loss},
keywords = {DNA methylation},
title = {DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease},
doi = {10.3390/biomedicines9111530},
author = {Flook, Marisa and Escalera Balsera, Alba and Gallego Martinez, Álvaro and Espinosa Sánchez, Juan Manuel and Aran, Ismael and Soto Varela, Andrés and López Escámez, José Antonio},
}