Intronic variants in the NFKB1 gene may influence hearing forecast in patients with unilateral sensorineural hearing loss in Meniere's disease.
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.
Otology & Neurotology Group CTS495, Department of Genomic Medicine- Centro de Genómica e Investigación Oncológica - Pfizer/Universidad de Granada/Junta de Andalucía (GENYO), Granada, Spain.
Sonia
S
Cabrera
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
Elena
E
Sanchez
Otology & Neurotology Group CTS495, Department of Genomic Medicine- Centro de Genómica e Investigación Oncológica - Pfizer/Universidad de Granada/Junta de Andalucía (GENYO), Granada, Spain.
Teresa
T
Requena
Group of Genetics of Complex Diseases, Department of Genomic Medicine - Centro de Genómica e Investigación Oncológica - Pfizer/Universidad de Granada/Junta de Andalucía (GENYO), Granada, Spain.
Manuel
M
Martinez-Bueno
Department of Otolaryngology, Hospital Universitario de Gran Canaria Dr Negrin, Las Palmas, Spain.
Jesus
J
Benitez
Department of Otolaryngology, Clinica Universidad de Navarra, Pamplona, Spain.
Nicolas
N
Perez
Division of Otoneurology, Department of Otorhinolaryngology, Complejo Hospitalario Badajoz, Badajoz, Spain.
Gabriel
G
Trinidad
Division of Otoneurology, Department of Otorhinolaryngology, Complexo Hospitalario Universitario, Santiago de Compostela, Spain.
Andrés
A
Soto-Varela
Division of Otoneurology, Department of Otorhinolaryngology, Complexo Hospitalario Universitario, Santiago de Compostela, Spain.
Sofía
S
Santos-Perez
Department of Otolaryngology, Hospital Universitario de Getafe, Getafe, Spain.
Eduardo
E
Martin-Sanz
Department of Otolaryngology, Hospital Miguel Servet, Zaragoza, Spain.
Jesus
J
Fraile
Department of Otorhinolaryngology, Hospital Cabueñes, Gijón, Spain.
Paz
P
Perez
Group of Genetics of Complex Diseases, Department of Genomic Medicine - Centro de Genómica e Investigación Oncológica - Pfizer/Universidad de Granada/Junta de Andalucía (GENYO), Granada, Spain.
Marta E
ME
Alarcon-Riquelme
Department of Otolaryngology, Hospital Universitario Salamanca, Salamanca, Spain.
Angel
A
Batuecas
Otology & Neurotology Group CTS495, Department of Genomic Medicine- Centro de Genómica e Investigación Oncológica - Pfizer/Universidad de Granada/Junta de Andalucía (GENYO), Granada, Spain; Department of Otorhinolaryngology, Hospital San Agustin, Linares, Jaen, Spain.
Juan M
JM
Espinosa-Sanchez
Department of Otolaryngology, Complexo Hospitalario de Pontevedra, Pontevedra, Spain.
Ismael
I
Aran
Otology & Neurotology Group CTS495, Department of Genomic Medicine- Centro de Genómica e Investigación Oncológica - Pfizer/Universidad de Granada/Junta de Andalucía (GENYO), Granada, Spain; Department of Otolaryngology, Hospital de Poniente, El Ejido, Almería, Spain.
Jose A
JA
Lopez-Escamez
D000483:Alleles; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006309:Hearing / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D007438:Introns / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008575:Meniere Disease / Q000235:genetics* / Q000503:physiopathology*; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human