Flook, MarisaEscalera-Balsera, AlbaGallego-Martinez, AlvaroEspinosa-Sanchez, Juan ManuelAran, IsmaelSoto-Varela, AndresLopez-Escamez, Jose Antonio2022-09-232022-09-232021-10-25Flook M, Escalera-Balsera A, Gallego-Martinez A, Espinosa-Sanchez JM, Aran I, Soto-Varela A, et al. DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease. Biomedicines. 2021 Oct 25;9(11):1530http://hdl.handle.net/10668/4116Meniere 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.enAtribución 4.0 InternacionalAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Meniere diseaseCytokinesWGBSHearing lossDNA methylationEnfermedad de MeniereCitocinasSecuenciación completa del genomaPérdida auditivaMetilación de ADNMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Base Sequence::GC Rich Sequence::CpG IslandsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA MethylationMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Acidic::Aspartic Acid::N-MethylaspartateMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Computational BiologyMedical Subject Headings::Diseases::Otorhinolaryngologic Diseases::Ear Diseases::Labyrinth Diseases::Endolymphatic Hydrops::Meniere DiseaseMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Membrane Potentials::Synaptic Potentials::Excitatory Postsynaptic PotentialsMedical Subject Headings::Diseases::Otorhinolaryngologic Diseases::Ear Diseases::Hearing Disorders::Hearing LossMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Acidic::GlutamatesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Regulatory Sequences, Nucleic Acidresearch article34829759open access10.3390/biomedicines91115302227-9059PMC8615058