RT Journal Article
T1 DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease.
A1 Flook, Marisa
A1 Escalera-Balsera, Alba
A1 Gallego-Martinez, Alvaro
A1 Espinosa-Sanchez, Juan Manuel
A1 Aran, Ismael
A1 Soto-Varela, Andres
A1 Lopez-Escamez, Jose Antonio
K1 DNA methylation
K1 Meniere Disease
K1 WGBS
K1 cytokines
K1 hearing loss
AB 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.
SN 2227-9059
YR 2021
FD 2021-10-25
LK https://hdl.handle.net/10668/26463
UL https://hdl.handle.net/10668/26463
LA en
DS RISalud
RD Apr 7, 2025