title: Functional variants of MIF, INFG and TFNA genes are not associated with disease susceptibility or hearing loss progression in patients with Ménière's disease.
abstract: Variability in acute immune response genes could determine susceptibility or prognosis for Ménière's disease (MD). The cytokines tumor necrosis factor α (TNFα), macrophage migration inhibitory factor (MIF) and interferon γ (INFγ) are proinflammatory cytokines of the innate immune response. These cytokines mediate inflammation and have been previously associated with the inflammatory process in several autoimmune diseases. We investigated the association between functional allelic variants of MIF (rs35688089), IFNG (rs2234688) and TNFA (rs1800629) in patients with MD. In addition to testing these variants for an association with disease, we also tested for an association with clinical aspects of disease progression, such as persistence of vertigo and the sensorineural hearing loss. A total of 580 patients with diagnosis of definite MD, according to the diagnostic scale of the American Academy of Otolaryngology-Head and Neck Surgery, and 552 healthy controls were included. DNA samples from a set of 291 American patients were used to confirm the results obtained in the MIF gene in our Spanish cohort. Although we found a significant association with the allele containing five repeats of CATT within the MIF gene in patients with MD in the Spanish cohort [corrected p = 0.008, OR = 0.69 (95 % CI, 0.54-0.88)], this finding could not be replicated in the American set. Moreover, no genetic associations for variants in either the TNFA or IFNG genes and MD were found. These results support the conclusion that functional variants of MIF, INFG, and TFNA genes are not associated with disease susceptibility or hearing loss progression in patients with MD.
authors.affiliation: Otology and Neurotology Group CTS495, Centro de Genómica e Investigación Oncológica Pfizer-Universidad de Granada-Junta de Andalucía (GENyO), Avda. de la Ilustración, 114, 18014 Granada, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Gázquez
authors.forename: Antonia
authors.initials: A
authors.lastname: Moreno
authors.forename: Teresa
authors.initials: T
authors.lastname: Requena
authors.forename: Jeff
authors.initials: J
authors.lastname: Ohmen
authors.forename: Sofia
authors.initials: S
authors.lastname: Santos-Perez
authors.forename: Ismael
authors.initials: I
authors.lastname: Aran
authors.forename: Andres
authors.initials: A
authors.lastname: Soto-Varela
authors.forename: Herminio
authors.initials: H
authors.lastname: Pérez-Garrigues
authors.forename: Alicia
authors.initials: A
authors.lastname: López-Nevot
authors.forename: Angel
authors.initials: A
authors.lastname: Batuecas
authors.forename: Rick A
authors.initials: RA
authors.lastname: Friedman
authors.forename: Miguel A
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: Jose A
authors.initials: JA
authors.lastname: López-Escamez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D003431:Cross-Cultural Comparison; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D008575:Meniere Disease / Q000235:genetics*; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013030:Spain; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014481:United States; D055815:Young Adult
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C069261:interferon gamma (1-39); D007371:Interferon-gamma; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human