MICA-STR A.4 Is Associated With Slower Hearing Loss Progression in Patients With Ménière’s Disease

Gázquez, Irene; Moreno, Antonia Ruíz; Arán, Ismael; Soto-Varela, Andrés; Santos, S. A.; Pérez-Garrigues, Herminio; López-Nevot, Alicia; Requena, Teresa; López–Nevot, Miguel A.; Lopez-Escamez, José A.

doi:10.1097/mao.0b013e31824296c8

Cited by 35 publications

(24 citation statements)

References 28 publications

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“…In our study, MICA*A6 was the most common allele in controls and patients; these results can also be observed in other studies from southern Spain [30,57]. In our UC patients there were no differences in MICA*A6 frequency among patients and controls.…”

Section: Discussionsupporting

confidence: 77%

MICAA4 protects against ulcerative colitis, whereas MICAA5.1 is associated with abscess formation and age of onset

Martínez-Chamorro

Moreno

Gómez‐García

et al. 2016

Clinical and Experimental Immunology

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SummaryUlcerative colitis (UC) is one of the two major forms of inflammatory bowel disease, the aetiology of which remains unknown. Several studies have demonstrated the genetic basis of disease, identifying more than 130 susceptibility loci. The major histocompatibility complex class I chainrelated gene A (MICA) is a useful candidate to be involved in UC pathogenesis, because it could be important in recognizing the integrity of the epithelial cell and its response to stress. The aim of this study was to analyse the relationship between polymorphisms in the transmembrane domain of MICA and susceptibility to develop UC. A total of 340 patients with UC and 636 healthy controls were genotyped for MICA transmembrane polymorphism using a polymerase chain reaction (PCR) combined with fluorescent technology. Different MICA alleles were determined depending on the PCR product size. The allele MICA*A4 was less frequent in patients than in controls (P 5 0Á003; OR 5 0Á643), and this protective role is higher when it forms haplotype with B*27 (P 5 0Á002; OR 5 0Á294). The haplotype HLA-B*52/MICA*A6 was also associated with UC [P 5 0Á001; odds ratio (OR) 5 2Á914]. No other alleles, genotypes or haplotypes were related with UC risk. Moreover, MICA*A5.1 is associated independently with abscesses (P 5 0Á002; OR 5 3Á096) and its frequency is lower in patients diagnosed between ages 17 and 40 years (P 5 0Á007; OR 5 0Á633), meaning an extreme age on onset. No association with location, extra-intestinal manifestations or need for surgery was found.

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Section: Discussionsupporting

confidence: 77%

MICAA4 protects against ulcerative colitis, whereas MICAA5.1 is associated with abscess formation and age of onset

Martínez-Chamorro

Moreno

Gómez‐García

et al. 2016

Clinical and Experimental Immunology

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“…Autoimmunity and human leucocyte antigen (HLA) associations were focused on early investigations into the causes of MD [22,23]. It has been shown that some major histocompatibility complexes (MHCs) and HLAs were related to MD, supporting that the autoimmune mechanism might be involved in the pathogenesis of MD [26,27]. It has been shown that some major histocompatibility complexes (MHCs) and HLAs were related to MD, supporting that the autoimmune mechanism might be involved in the pathogenesis of MD [26,27].…”

Section: Introductionmentioning

confidence: 99%

“…Studies found that the frequency of human leucocyte antigen (HLA)Cw*04, HLA-DRB1*1101 and the allelic group HLA-DRB1*11 might suggest an increased susceptibility to develop MD [22,24,25]. It has been shown that some major histocompatibility complexes (MHCs) and HLAs were related to MD, supporting that the autoimmune mechanism might be involved in the pathogenesis of MD [26,27]. Intratympanic injection of dexamethasone has been adapted as an anti-immune or antiinflammatory therapy for patients with intractable MD, which preserved the inner ear function probably by its antiinflammatory and ion-homeostatic effects [17,28,29].…”

Section: Introductionmentioning

confidence: 99%

RNA-sequencing study of peripheral blood mononuclear cells in sporadic Ménière's disease patients: possible contribution of immunologic dysfunction to the development of this disorder

Sun

Zhang

Sun

et al. 2017

Clinical and Experimental Immunology

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To date, the pathogenesis of Ménière's disease (MD) remains unclear. This study aims to investigate the possible relationship between potential immune system-related genes and sporadic MD. The whole RNA-sequencing (RNA-seq) technology was used to analyse the transcriptome of peripheral blood mononuclear cells of three MD patients and three control individuals. Of 366 differentially expressed genes (DEGs), 154 genes were up-regulated and 212 genes were down-regulated (|log fold change| > 1 and P < 0·05). Gene ontology (GO) enrichment analysis illustrated that immune relevant factors played a key role in the pathogenesis of MD. Of 366 DEGs, we focused upon analysing the possible immune-related genes, among which the significantly up-regulated genes [glutathione S-transferase mu 1 (GSTM1), transmembrane protein 176 (TMEM176)B, TMEM176A] and down-regulated genes [solute carrier family 4 member (SLC4A)10 and SLC4A1] especially drew our attention. The mRNA expression levels of GSTM1, TMEM176B, TMEM176A, SLC4A1 and SLC4A10 were analysed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The serum concentration of GSTM1, TMEM176B and SLC4A10 proteins were measured by enzyme-linked immunosorbent assay (ELISA). Considering the results of qRT-PCR and ELISA, it was noteworthy that GSTM1 exhibited the highest fold change between two groups, which was consistent with the deep sequencing results by RNA-seq. In conclusion, our study first offers a new perspective in MD development on the basis of RNA expression patterns, suggesting that immune factors might be involved in the MD pathogenesis. Remarkably, GSTM1 might be a possible candidate gene for the diagnostic biomarker of MD and provides the basis for further biological and functional investigations.

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“…Therefore, allelic variations in the MICA, NFKB1 or TLR10 genes have been reported to influence the hearing loss outcome in patients with sporadic MD. [27][28][29] Third, several relatives in these families presented a partial syndrome with different types of SNHL, including sudden hearing loss (III: 2 in family 2) or pantonal SNHL (II: 2 in family 2) and no vestibular symptoms. These findings observed across different families with MD 12,14,15 suggests that (1) different genes can be involved in the development of the partial or complete phenotype or (2) the interaction of environmental or epigenetic factors can also determine the differences in expressivity within the phenotype.…”

Section: Discussionmentioning

confidence: 97%

Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere’s disease

et al. 2016

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Autosomal dominant (AD) familial Meniere's disease (FMD) is a rare disorder involving the inner ear defined by sensorineural hearing loss, tinnitus and episodic vertigo. Here, we have identified two novel and rare heterozygous variants in the SEMA3D and DPT genes segregating with the complete phenotype that have variable expressivity in two pedigrees with AD-FMD. A detailed characterization of the phenotype within each family illustrates the clinical heterogeneity in the onset and progression of the disease. We also showed the expression of both genes in the human cochlea and performed in silico analyses of these variants. Three-dimensional protein modelling showed changes in the structure of the protein indicating potential physical interactions. These results confirm a genetic heterogeneity in FMD with incomplete penetrance and variable expressivity.

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MICA-STR A.4 Is Associated With Slower Hearing Loss Progression in Patients With Ménière’s Disease

Abstract: The allelic variant MICA*A.4 is significantly associated with slower progression of hearing loss in patients with MD. This suggests that the immune response influence hearing level in MD.

Cited by 35 publications

References 28 publications

MICAA4 protects against ulcerative colitis, whereas MICAA5.1 is associated with abscess formation and age of onset

MICAA4 protects against ulcerative colitis, whereas MICAA5.1 is associated with abscess formation and age of onset

RNA-sequencing study of peripheral blood mononuclear cells in sporadic Ménière's disease patients: possible contribution of immunologic dysfunction to the development of this disorder

Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere’s disease

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MICA-STR A.4 Is Associated With Slower Hearing Loss Progression in Patients With Ménière’s Disease

Abstract: The allelic variant MICA*A.4 is significantly associated with slower progression of hearing loss in patients with MD. This suggests that the immune response influence hearing level in MD.

Cited by 35 publications

References 28 publications

MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset

MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset

RNA-sequencing study of peripheral blood mononuclear cells in sporadic Ménière's disease patients: possible contribution of immunologic dysfunction to the development of this disorder

Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere’s disease

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MICAA4 protects against ulcerative colitis, whereas MICAA5.1 is associated with abscess formation and age of onset

MICAA4 protects against ulcerative colitis, whereas MICAA5.1 is associated with abscess formation and age of onset