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

Flook, Marisa; Escalera‐Balsera, Alba; Gallego‐Martinez, Alvaro; Espinosa-Sánchez, Juan Manuel; Arán, Ismael; Soto-Varela, Andrés; Lopez-Escamez, José A.

doi:10.3390/biomedicines9111530

Cited by 15 publications

(13 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A pilot epigenomic study was performed using whole-genome bisulfite sequencing (WGBS) suggesting that the DNA methylation signature could allow distinguishing between Meniere's disease patients and controls [35]. In this study, a great number of differentially methylated CpGs were found when comparing Meniere's disease patients to controls.…”

Section: Epigenetics and Meniere's Diseasementioning

confidence: 89%

Epidemiology and genetics of Meniere's disease

Lopez-Escamez,

Liu

2023

Current Opinion in Neurology

View full text Add to dashboard Cite

Purpose of review This review discusses the recent developments on the understanding of epidemiology and genetics of Meniere's disease. Recent findings Meniere's disease has been shown to be associated with several comorbidities, such as migraine, anxiety, allergy and immune disorders. Recent studies have investigated the relationship between environmental factors and Meniere's disease such as air pollution, allergy, asthma, osteoporosis or atmospheric pressure, reporting specific comorbidities in East Asian population. The application of exome sequencing has enabled the identification of genes sharing rare missense variants in multiple families with Meniere's disease, including OTOG and TECTA and suggesting digenic inheritance in MYO7A. Moreover, knockdown of DTNA gene orthologue in Drosophila resulted in defective proprioception and auditory function. DTNA and FAM136A knockout mice have been studied as potential mouse models for Meniere's disease. Summary While it has attracted emerging attention in recent years, the study of Meniere's disease genetics is still at its early stage. More geographically and ethnically based human genome studies, and the development of cellular and animal models of Meniere's disease may help shed light on the molecular mechanisms of Meniere's disease and provide the potential for gene-specific therapies.

show abstract

Section: Epigenetics and Meniere's Diseasementioning

confidence: 89%

Epidemiology and genetics of Meniere's disease

Lopez-Escamez,

Liu

2023

Current Opinion in Neurology

View full text Add to dashboard Cite

show abstract

“…were determined as differentially methylated when comparing MD against healthy controls. Those genes encode for stereocilia link proteins, which are involved in attaching the hair cells to the TM 11 .…”

Section: Discussionmentioning

confidence: 99%

“…By whole-genome bisulfite sequencing (WGBS), CpGs in ADGRV1 (MIM: 602851), CDH23 (MIM: 605516) and PCDH15 (MIM: 605514) were determined as differentially methylated when comparing MD against healthy controls. Those genes encode for stereocilia link proteins, which are involved in attaching the hair cells to the TM 11 .…”

Section: Discussionmentioning

confidence: 99%

“…The criteria to diagnose MD are based on the clinical symptoms occurring during the attacks of vertigo and the documentation of SNHL by pure tone audiogram before, during, or after the episode of vertigo. Several subgroups of patients with MD have been reported according to associated co-morbidities 9 , such as migraine or autoimmune disorders, cytokine profile 10 or methylation signature 11 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A rare haplotype of theGJD3gene segregating in familial Meniere Disease interferes with connexin assembly

Escalera-Balsera,

Robles-Bolivar,

Parra-Perez

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Familial Meniere Disease (FMD) is a rare polygenic disorder of the inner ear. Mutations in the connexin gene family, which encodes gap junction proteins, can also cause hearing loss, but their role in FMD is largely unknown. Here, we found an enrichment of rare missense variants in the GJD3 gene when comparing allelic frequencies in FMD (N=94) with the Spanish reference population (OR=3.9[1.92-7.91], FDR=2.36E-03). In the GJD3 sequence, we identified a rare haplotype (TGAGT) composed of two missense, two synonymous, and one downstream variants. This haplotype was found in five individuals with FMD, segregating in three unrelated families with a total of ten individuals; and in another eight Meniere Disease individuals. GJD3 encodes the gap junction protein delta 3, also known as human connexin 31.9 (CX31.9). The protein model predicted that the NP_689343.3:p.(His175Tyr) missense variant could modify the interaction between connexins and the connexon assembly, affecting the homotypic GJD3 gap junction between cells. Our studies in mice revealed that the mouse ortholog Gjd3 - encoding Gjd3 or mouse connexin 30.2 (Cx30.2) - was expressed in the organ of Corti and vestibular organs, particularly in the tectorial membrane, the base of inner and outer hair cells and the nerve fibers. The present results describe a novel association between GJD3 and familial FMD, providing evidence that FMD is related to changes in the inner ear channels; in addition, it supports a new role of tectorial membrane proteins in FMD.

show abstract

“…Similarly, several studies have described an autoimmune or autoin ammatory role in MD within the past decade [21][22][23][24][25][26] . Different methylation patterns between MD patients and controls have been reported 25 , as well as differentiation of 2 subgroups of MD patients according to the baseline levels of IL-1β (High and low), leading to different immune response pro les to antigens that re ect the functional status of the immune system 22 . Moreover, differential expression of many proin ammatory cytokines such as IL-1β, CCL3, CCL18, CCL22, CXCL1, and CXCL4 has been able to differentiate between MD and vestibular migraine 23 and migraine 24 .…”

Section: Introductionmentioning

confidence: 99%

Allergy and autoinflammation drive persistent systemic inflammatory response in Meniere Disease

Frejo,

Cara,

Flook

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Meniere disease (MD) is an inner ear disorder associated with genetic and environmental factors. Several triggers may induce an inflammatory response that may persist over time, leading to a chronic inflammatory process. This study aims to determine if the inflammatory state observed in some MD patients is mediated by allergy or autoinflammation. A 2-year longitudinal study including 72 patients was designed to track levels of cytokines and chemokines in plasma samples. We used discriminant and trajectory analyses to define functional clusters. Furthermore, THP-1 cells were treated with MD patients’ plasma and NaCl to study their capacity to polarize to M1 or M2 macrophages, and qPCR was used to study the upstream events leading to cytokine release. We identified 4 groups of patients according to their cytokine levels. First, an autoimmune group with high TNF-α levels (19%). An allergic phenotype (24%) with elevated IgE and the capacity to polarize macrophages into M2. The third with an autoinflammatory phenotype had increased IL-1β (14%) activated through CASP1 and NLRP3. The last group had low levels of cytokines (42%). Most individuals remained in the same group according to their cytokine levels over time; interestingly, 36% of patients with an allergic profile also showed high levels of IL-1β. We characterized 2 immunophenotypes according to cytokines and IgE levels. The first may drive an allergic reaction led by IgE and classical allergy-related cytokines. A second group of patients seems to be mediated by the production of IL-1β and the inflammasome pathway.

show abstract

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

Cited by 15 publications

References 68 publications

Epidemiology and genetics of Meniere's disease

Epidemiology and genetics of Meniere's disease

A rare haplotype of theGJD3gene segregating in familial Meniere Disease interferes with connexin assembly

Allergy and autoinflammation drive persistent systemic inflammatory response in Meniere Disease

Contact Info

Product

Resources

About