Meniere’s Disease: Genetics and the Immune System

Flook, Marisa; Lopez-Escamez, José A.

doi:10.1007/s40136-018-0182-8

Cited by 14 publications

(9 citation statements)

References 72 publications

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“…While most of the incidence of MD is considered sporadic, about a third of those with MD exhibit evidence of pro-inflammatory cytokine mediated immune dysfunction [3, 5, 12]. About 5% of cases of MD show evidence of heritability, and in such cases NF-κB mediated inflammation appears influential [13]. Overall, several lines of epidemiological evidence suggest that between various MD clinical sub-groups, inflammatory signatures and immunotype changes in the inner-ear are common [12, 13].…”

Section: Introductionmentioning

confidence: 99%

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Are viral-infections associated with Ménière’s Disease? A systematic review and meta-analysis of molecular-markers of viral-infection in case-controlled observational studies of MD

et al. 2019

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Despite considerable research, it remains controversial as to whether viral-infections are associated with Meniere’s Disease (MD), a clinically heterogeneous set of chronic inner-ear disorders strongly associated with endolymphatic hydrops. Here, we investigated whether viral-infections are associated with MD through a systematic review and meta-analysis of observational clinical studies using molecular-diagnostics. Eligible for inclusion were case-controlled studies which ascertained molecular-determinants of past or present viral-infection through either viral nucleic acids or host serological marker in MD cases and non-MD controls. Across online databases and grey literature, we identified 210 potentially relevant articles in the English language, from which a total of 14 articles fully satisfied our eligibility criteria such that meta-groups of 611 MD-cases and 373 controls resulted. The aggregate quality of the modest-sized (14 studies) body of evidence was limited and varied considerably with regards to participant selection, matching, and ascertainment(s) and determinant(s) of viral-infection. Most data identified concerned the human cytomegalovirus (CMV), and meta-analysis of eligible studies revealed that evidence of CMV-infection was associated approximately three-fold with MD compared to controls, however the timing of the infections was indeterminate as the pooled analyses combined antiviral serological markers with viral nucleic acid markers. No association was found for any of HSV-1, -2, VZV, or EBV. Associative analyses of any viral species not aforementioned were precluded by limited data, and thus potential associations between other viral species and MD, especially other than Herpesviridae, are yet to be characterised. Overall, we have found a small association between CMV-infection and MD, however it is to be determined for what sub-groups of MD this finding may be relevant, and ideally the reported association remains would be reproduced by a greater volume of higher quality evidence.

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Section: Introductionmentioning

confidence: 99%

“…About 5% of cases of MD show evidence of heritability, and in such cases NF-κB mediated inflammation appears influential [13]. Overall, several lines of epidemiological evidence suggest that between various MD clinical sub-groups, inflammatory signatures and immunotype changes in the inner-ear are common [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Are viral-infections associated with Ménière’s Disease? A systematic review and meta-analysis of molecular-markers of viral-infection in case-controlled observational studies of MD

et al. 2019

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“…9,10 This has supported the hypothesis of an innate immune dysfunction in certain patients with MD. 11 An allelic variant has been identified in 6p21.33 (leading signal rs4947296) associated with bilateral MD. 12 So, certain MD patients with this genetic marker should be considered as autoimmune MD.…”

mentioning

confidence: 99%

Current Understanding and Clinical Management of Meniere's Disease: A Systematic Review

Pérez-Carpena

Lopez-Escamez

2019

Semin Neurol

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Meniere's disease (MD) is a set of uncommon disorders with core phenotype of tinnitus, episodic vertigo, and sensorineural hearing loss. MD shows a genetic predisposition and a family history is found in 10% cases, with an autosomal dominant inheritance pattern. It is a multifactorial condition whose onset and development are triggered by the combined effect of genetic and environmental factors. Histopathological studies have associated MD with the accumulation of endolymph in the cochlea and the vestibular organs. However, endolymphatic hydrops does not fully explain the persistence of tinnitus, hearing loss progression, or the frequency of vertigo attacks.There are several comorbidities associated with MD, such as migraine, anxiety, autoimmune, and autoinflammatory disorders, adding more complexity to the phenotype. This “extended phenotype” can make the diagnosis and clinical management more complex, but it could also lead to a better characterization, understanding, and treatment of MD patients.We have conducted a systematic review on MD to update current knowledge, focusing on its mechanisms, diagnosis, comorbidities, and practical management.

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“…Several lines of epidemiological evidence support a genetic contribution in MD, including (a) the higher prevalence observed in the European population over other ethnicities 16 and (b) a strong familial aggregation found in Europeans and South Koreans ranging from 6% to 10% of cases with a high sibling recurrence risk ratio ( λs = 24–45) 18 , 19 , 23 – 25 .…”

Section: Evidence For a Genetic Contribution To Ménière’s Diseasementioning

confidence: 98%

Towards personalized medicine in Ménière’s disease

2018

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Ménière’s disease (MD) represents a heterogeneous group of relatively rare disorders with three core symptoms: episodic vertigo, tinnitus, and sensorineural hearing loss involving 125 to 2,000 Hz frequencies. The majority of cases are considered sporadic, although familial aggregation has been recognized in European and Korean populations, and the search for familial MD genes has been elusive until the last few years. Detailed phenotyping and cluster analyses have found several clinical predictors for different subgroups of patients, which may indicate different mechanisms, including genetic and immune factors. The genes associated with familial MD are COCH, FAM136A, DTNA, PRKCB, SEMA3D, and DPT. At least two mechanisms have been involved in MD: (a) a pro-inflammatory immune response mediated by interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα), and IL-6, and (b) a nuclear factor-kappa B (NF-κB)-mediated inflammation in the carriers of the single-nucleotide variant rs4947296. It is conceivable that microbial antigens trigger inflammation with release of pro-inflammatory cytokines at different sites within the cochlea, such as the endolymphatic sac, the stria vascularis, or the spiral ligament, leading to fluid imbalance with an accumulation of endolymph. Computational integration of clinical and “omics” data eventually should transform the management of MD from “one pill fits all” to precise patient stratification and a personalized approach. This article lays out a proposal for an algorithm for the genetic diagnosis of MD. This approach will facilitate the identification of new molecular targets for individualized treatment, including immunosuppressant and gene therapy, in the near future.

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Meniere’s Disease: Genetics and the Immune System

Cited by 14 publications

References 72 publications

Are viral-infections associated with Ménière’s Disease? A systematic review and meta-analysis of molecular-markers of viral-infection in case-controlled observational studies of MD

Are viral-infections associated with Ménière’s Disease? A systematic review and meta-analysis of molecular-markers of viral-infection in case-controlled observational studies of MD

Current Understanding and Clinical Management of Meniere's Disease: A Systematic Review

Towards personalized medicine in Ménière’s disease

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