المؤلفون: Lidia Frejo, Teresa Requena, Satoshi Okawa, Alvaro Gallego-Martinez, Manuel Martinez-Bueno, Ismael Aran, Angel Batuecas-Caletrio, Jesus Benitez-Rosario, Juan M. Espinosa-Sanchez, Jesus José Fraile-Rodrigo, Ana María García-Arumi, Rocío González-Aguado, Pedro Marques, Eduardo Martin-Sanz, Nicolas Perez-Fernandez, Paz Pérez-Vázquez, Herminio Perez-Garrigues, Sofía Santos-Perez, Andres Soto-Varela, Maria C. Tapia, Gabriel Trinidad-Ruiz, Antonio del Sol, Marta E. Alarcon Riquelme, Jose A. Lopez-Escamez

المصدر: Frontiers in Immunology, Vol 8 (2017)

مصطلحات موضوعية: TNFRSF12A, NFKB1, TWEAK/Fn14 pathway, NF-κB signaling, vertigo, sensorineural hearing loss, Immunologic diseases. Allergy, RC581-607

الوصف: Meniere’s disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case–control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661–2.627); p = 1.39 × 10−09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10−11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD.

وصف الملف: electronic resource

العلاقة: http://journal.frontiersin.org/article/10.3389/fimmu.2017.01739/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/a86c95ab29ac42fd8cc2abfac84165b8Test

المؤلفون: Frejo, Lidia, Requena, Teresa, Satoshi Okawa, Gallego-Martinez, Alvaro, Martinez-Bueno, Manuel, Aran, Ismael, Batuecas-Caletrio, Angel, Benitez-Rosario, Jesus, Espinosa-Sanchez, Juan M., Fraile-Rodrigo, Jesus José, García-Arumi, Ana María, González-Aguado, Rocío, Marques, Pedro, Martin-Sanz, Eduardo, Perez-Fernandez, Nicolas, Pérez-Vázquez, Paz, Perez-Garrigues, Herminio, Santos-Perez, Sofía, Soto-Varela, Andres, Tapia, Maria C.

المصدر: Frontiers in Immunology; 12/13/2017, p1-15, 15p

مصطلحات موضوعية: MENIERE'S disease, NF-kappa B, FIBROBLAST growth factor receptors

مستخلص: Meniere's disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case-control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661-2.627); p = 1.39 × 10^-09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10^-11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD. [ABSTRACT FROM AUTHOR]

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