Flook Marisa, Escalera-Balsera Alba, Gallego-Martinez Alvaro, Espinosa-Sanchez Juan Manuel, Aran Ismael, Soto-Varela Andres, Lopez-Escamez Jose Antonio
Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO, Centre for Genomics and Oncological Research, Pfizer University of Granada Andalusian Regional Government, PTS, 18016 Granada, Spain.
Sensorineural Pathology Programme, Centro de Investigación Biomédica en Red en Enfermedades Raras, CIBERER, 28029 Madrid, Spain.
Biomedicines. 2021 Oct 25;9(11):1530. 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.
梅尼埃病（MD）是一种内耳的多因素疾病，其特征为眩晕发作，并伴有感音神经性听力损失和耳鸣，具有显著的遗传力。尽管MD已与多个基因相关联，但尚未对MD进行表观遗传学研究。在此，我们对14例MD患者和6名健康对照进行了全基因组亚硫酸氢盐测序，旨在识别MD甲基化特征和潜在的疾病机制。在将MD患者与对照进行比较时，我们观察到大量差异甲基化的CpG（DMC）（= 9545个），其中一些位于听力损失相关基因中，如 和 。将MD与对照进行比较时，对DMC和顺式调控区域的生物信息学分析预测了与异常兴奋性突触后电流、异常NMDA介导的受体电流和异常谷氨酸介导的受体电流相关的表型。此外，我们在先前与小鼠耳蜗前庭表型相关的基因中鉴定出了各种DMC。我们还发现了12个MD特有的低甲基化区域（UMR），包括 基因中一个CpG岛间的两个UMR。我们认为，DNA甲基化特征能够区分MD患者和对照。富集分析证实了先前关于MD潜在慢性炎症过程的研究结果。
