DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease Flook, Marisa Escalera Balsera, Alba Gallego Martinez, Álvaro Espinosa Sánchez, Juan Manuel Aran, Ismael Soto Varela, Andrés López Escámez, José Antonio Meniere Disease Cytokines WGBS Hearing loss DNA methylation 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. 2021-11-03T07:42:35Z 2021-11-03T07:42:35Z 2021 info:eu-repo/semantics/article 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. https://doi.org/10.3390/ biomedicines9111530 http://hdl.handle.net/10481/71234 10.3390/biomedicines9111530 eng eu-repo/grantAgreement/EC/H2020/848261 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI