RT Journal Article
T1 Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere's Disease.
A1 Frejo, Lidia
A1 Requena, Teresa
A1 Okawa, Satoshi
A1 Gallego-Martinez, Alvaro
A1 Martinez-Bueno, Manuel
A1 Aran, Ismael
A1 Batuecas-Caletrio, Angel
A1 Benitez-Rosario, Jesus
A1 Espinosa-Sanchez, Juan M
A1 Fraile-Rodrigo, Jesus José
A1 García-Arumi, Ana María
A1 González-Aguado, Rocío
A1 Marques, Pedro
A1 Martin-Sanz, Eduardo
A1 Perez-Fernandez, Nicolas
A1 Pérez-Vázquez, Paz
A1 Perez-Garrigues, Herminio
A1 Santos-Perez, Sofía
A1 Soto-Varela, Andres
A1 Tapia, Maria C
A1 Trinidad-Ruiz, Gabriel
A1 Del Sol, Antonio
A1 Alarcon Riquelme, Marta E
A1 Lopez-Escamez, Jose A
K1 Meniere’s disease
K1 NF-κB signaling
K1 NFKB1
K1 TNFRSF12A
K1 TWEAK/Fn14 pathway
K1 sensorineural hearing loss
K1 vertigo
AB 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.
SN 1664-3224
YR 2017
FD 2017-12-13
LK http://hdl.handle.net/10668/11996
UL http://hdl.handle.net/10668/11996
LA en
DS RISalud
RD Apr 7, 2025