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

• Published in: Biomedicines Vol. 9; no. 11; p. 1530
• Main Authors: Flook, Marisa, Escalera-Balsera, Alba, Gallego-Martinez, Alvaro, Espinosa-Sanchez, Juan Manuel, Aran, Ismael, Soto-Varela, Andres, Lopez-Escamez, Jose Antonio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-10-2021; MDPI
• Subjects: Bias; Bisulfite; CpG islands; Cytokines; Deoxyribonucleic acid; DNA; DNA methylation; Ears & hearing; Epigenetics; Excitatory postsynaptic potentials; Gene expression; Genomes; Glutamic acid receptors (ionotropic); Hearing loss; Heritability; Inflammation; Inner ear; Leukocytes (mononuclear); Meniere Disease; Meniere's disease; N-Methyl-D-aspartic acid receptors; Phenotypes; Regulatory sequences; Tinnitus; Values; Vertigo; WGBS; United States > US; DNA methylation; WGBS; cytokines; hearing loss; Meniere Disease
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines9111530

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 (
= 9545), several of them in hearing loss genes, such as
and
. 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
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.