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Abstract <p>Meniere disease (MD) is a cochleo-vestibular syndrome defined by episodes of vertigo associated with tinnitus and sensorineural hearing loss. While MD immune response has been linked to autoinflammation and type 2 cytokines, other molecular mechanisms such as DNA methylation have an emerging yet underexplored role in MD pathophysiology.To understand the role of DNA methylation in MD, we performed whole-genome bisulphite sequencing in MD patients (<i>n</i> = 40) and controls (<i>n</i> = 13) and used differentially methylated cytosines (DMCs) to define clusters, cell types, and biochemical pathways in MD. We found three MD subclusters: Cluster 1 (40% of patients) and Cluster 3 (25%) showed DMC profiles against controls, while Cluster 2 (35%) did not. Significant DMCs from Cluster 1 and Cluster 3 versus Control analysis were annotated to 3033 and 59 unique genes, respectively. Each cluster showed a different gene enrichment; however, the <i>KDMB4</i> gene had significant upregulated DNA accessibility in a complementary ATAC-seq dataset and showed significant DMCs in both Cluster 1 and Cluster 3. DNA methylation patterns in MD reveal three clusters which are reflective of an underlying difference in pathways related to cytokine stimulus, immunity T-cell, and NK-cell pathways. <i>KDMB4</i> emerges as a critical MD gene which deserves further research.</p> Key messages <p><UnorderedList Mark="Bullet"> <ItemContent> <p>We asked if DNA methylation can help understand Meniere’s Disease (MD) pathophysiology.</p> </ItemContent> <ItemContent> <p>DNA methylomes group MD patients into three distinct sub-clusters.</p> </ItemContent> <ItemContent> <p>DNA methylation in MD reflect difference in pathways related to neurons and cytokine stimulus.</p> </ItemContent> <ItemContent> <p>The data shows <i>KDMB4</i> emerging as a key gene that requires further multi-modal investigation.</p> </ItemContent> </UnorderedList></p>

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Whole genome DNA methylation profiles define Meniere’s disease subclusters

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月6日

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  • Vibha Patil,
  • Pablo Cruz-Granados,
  • Francisca E. Cara,
  • Juan Carlos Amor-Dorado,
  • Ismael Aran,
  • Andres Soto-Varela,
  • Patricia Perez-Carpena,
  • Jose Antonio Lopez-Escamez

摘要

Abstract

Meniere disease (MD) is a cochleo-vestibular syndrome defined by episodes of vertigo associated with tinnitus and sensorineural hearing loss. While MD immune response has been linked to autoinflammation and type 2 cytokines, other molecular mechanisms such as DNA methylation have an emerging yet underexplored role in MD pathophysiology.To understand the role of DNA methylation in MD, we performed whole-genome bisulphite sequencing in MD patients (n = 40) and controls (n = 13) and used differentially methylated cytosines (DMCs) to define clusters, cell types, and biochemical pathways in MD. We found three MD subclusters: Cluster 1 (40% of patients) and Cluster 3 (25%) showed DMC profiles against controls, while Cluster 2 (35%) did not. Significant DMCs from Cluster 1 and Cluster 3 versus Control analysis were annotated to 3033 and 59 unique genes, respectively. Each cluster showed a different gene enrichment; however, the KDMB4 gene had significant upregulated DNA accessibility in a complementary ATAC-seq dataset and showed significant DMCs in both Cluster 1 and Cluster 3. DNA methylation patterns in MD reveal three clusters which are reflective of an underlying difference in pathways related to cytokine stimulus, immunity T-cell, and NK-cell pathways. KDMB4 emerges as a critical MD gene which deserves further research.

Key messages

We asked if DNA methylation can help understand Meniere’s Disease (MD) pathophysiology.

DNA methylomes group MD patients into three distinct sub-clusters.

DNA methylation in MD reflect difference in pathways related to neurons and cytokine stimulus.

The data shows KDMB4 emerging as a key gene that requires further multi-modal investigation.