Cabrera, SoniaSanchez, ElenaRequena, TeresaMartinez-Bueno, ManuelBenitez, JesusPerez, NicolasTrinidad, GabrielSoto-Varela, AndrésSantos-Perez, SofíaMartin-Sanz, EduardoFraile, JesusPerez, PazAlarcon-Riquelme, Marta EBatuecas, AngelEspinosa-Sanchez, Juan MAran, IsmaelLopez-Escamez, Jose A2015-11-192015-11-192014-11-14Cabrera S, Sanchez E, Requena T, Martinez-Bueno M, Benitez J, Perez N, et al. Intronic variants in the NFKB1 gene may influence hearing forecast in patients with unilateral sensorineural hearing loss in Meniere's disease. PLoS ONE 2014 ; 9(11):e112171http://hdl.handle.net/10668/2060Journal Article; Research Support, Non-U.S. Gov't;Meniere's disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-κB pathway, such as REL, TNFAIP3, NFKB1 and TNIP1, have been associated with two or more immune-mediated diseases and allelic variations in the TLR10 gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10(-8)), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and p = 0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL.enEnfermedad de MeniereDesequilibrio de LigamientoPolimorfismo de Nucleótido SimpleFN-kappa BMediana EdadHumanosFemeninoMasculinoEstimación de Kaplan-MeierIntronesPérdida AuditivaHaplotiposPredisposición Genética a la EnfermedadProgresión de la EnfermedadAlelosMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease ProgressionMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to DiseaseMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::HaplotypesMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Sensation Disorders::Hearing Disorders::Hearing LossMedical Subject Headings::Diseases::Otorhinolaryngologic Diseases::Ear Diseases::Hearing Disorders::Hearing Loss::Hearing Loss, SensorineuralMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::DNA, Intergenic::IntronsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis::Kaplan-Meier EstimateMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Linkage::Linkage DisequilibriumMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Diseases::Otorhinolaryngologic Diseases::Ear Diseases::Labyrinth Diseases::Endolymphatic Hydrops::Meniere DiseaseMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::NF-kappa B::NF-kappa B p50 SubunitMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Allelesresearch article25397881open access10.1371/journal.pone.01121711932-6203PMC4232390