DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease
| Autor: | Alvaro Gallego-Martinez, Jose A. Lopez-Escamez, Alba Escalera-Balsera, Andrés Soto-Varela, Marisa Flook, Ismael Aran, Juan Manuel Espinosa-Sanchez |
|---|---|
| Přispěvatelé: | [Flook,M, Escalera-Balsera,A, Gallego-Martinez,A, Espinosa-Sanchez,JM, Lopez-Escamez,JA] Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO, Centre for Genomics and Oncological Research, Pfizer University of Granada Andalusian Regional Government, PTS, Granada, Spain. [Flook,M, Lopez-Escamez,JA] Sensorineural Pathology Programme, Centro de Investigación Biomédica en Red en Enfermedades Raras, CIBERER, Madrid, Spain. [Flook,M, Lopez-Escamez,JA] Department of Otolaryngology, Instituto de Investigación Biosanitaria ibs.Granada, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain. [Aran,I] Department of Otolaryngology, Complexo Hospitalario de Pontevedra, Pontevedra, Spain. [Soto-Varela,A] Division of Otoneurology, Department of Otorhinolaryngology, Complexo Hospitalario Universitario, Santiago de Compostela, Spain. [Lopez-Escamez,JA] Division of Otolaryngology, Department of Surgery, University of Granada, Granada, Spain., This work was supported by PI17/1644 grant from ISCIII by FEDER Funds from the EU.MF is funded by F18/00228 grant from ISCIII by FEDER Funds from the EU. AEB is funded by the EU’s Horizon 2020 Research and Innovation Programme, Grant Agreement Number 848261. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings]
QH301-705.5 Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Regulatory Sequences Nucleic Acid [Medical Subject Headings] Bisulfite sequencing Medicine (miscellaneous) Biology Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Base Sequence::GC Rich Sequence::CpG Islands [Medical Subject Headings] Article General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine Secuenciación completa del genoma Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] WGBS Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Methylation [Medical Subject Headings] Organisms::Eukaryota::Animals [Medical Subject Headings] medicine otorhinolaryngologic diseases genetics Epigenetics Biology (General) Meniere Disease Diseases::Otorhinolaryngologic Diseases::Ear Diseases::Labyrinth Diseases::Endolymphatic Hydrops::Meniere Disease [Medical Subject Headings] hearing loss Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] DNA methylation Enfermedad de Meniere Citocinas Hearing loss Methylation Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Membrane Potentials::Synaptic Potentials::Excitatory Postsynaptic Potentials [Medical Subject Headings] medicine.disease Phenotype cytokines Chemicals and Drugs::Amino Acids Peptides and Proteins::Amino Acids::Amino Acids Acidic::Aspartic Acid::N-Methylaspartate [Medical Subject Headings] Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Computational Biology [Medical Subject Headings] CpG site Pérdida auditiva Meniere disease Diseases::Otorhinolaryngologic Diseases::Ear Diseases::Hearing Disorders::Hearing Loss [Medical Subject Headings] Cancer research Cytokines Sensorineural hearing loss Chemicals and Drugs::Amino Acids Peptides and Proteins::Amino Acids::Amino Acids Acidic::Glutamates [Medical Subject Headings] Metilación de ADN |
| Zdroj: | Biomedicines Volume 9 Issue 11 Biomedicines, Vol 9, Iss 1530, p 1530 (2021) Digibug. Repositorio Institucional de la Universidad de Granada Consorcio Madroño |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines9111530 |
| Popis: | 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. PI17/1644 grant from ISCIII by FEDER Funds from the EU F18/00228 grant from ISCIII by FEDER Funds from the EU AEB is funded by the EU’s Horizon 2020 Research and Innovation Programme, Grant Agreement Number 848261. |
| Databáze: | OpenAIRE |
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