Abstract
Chronic otitis media with effusion (COME) is the most common cause of hearing loss in children, and known to have high heritability. Mutant mouse models have identified Fbxo11, Evi1, Tgif1, and Nisch as potential risk loci. We recruited children aged 10 and under undergoing surgical treatment for COME from 35 hospitals in the UK, and their nuclear family. We performed association testing with the loci FBXO11, EVI1, TGIF1 and NISCH and sought to replicate significant results in a case-control cohort from Finland. We tested 1296 families (3828 individuals), and found strength of association with the T allele at rs881835 (p = 0.006, OR 1.39) and the G allele at rs1962914 (p = 0.007, OR 1.58) at TGIF1, and the A allele at rs10490302 (p = 0.016, OR 1.17) and the G allele at rs2537742 (p = 0.038, OR 1.16) at FBXO11. Results were not replicated. This study supports smaller studies that have also suggested association of otitis media with polymorphism at FBX011, but this is the first study to report association with the locus TGIF1. Both FBX011 and TGIF1 are involved in TGF-β signalling, suggesting this pathway may be important in the transition from acute to chronic middle ear inflammation, and a potential molecular target.
Publication types
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Animals
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Child
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Child, Preschool
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Chronic Disease
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Cohort Studies
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Disease Models, Animal
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F-Box Proteins / genetics*
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F-Box Proteins / metabolism
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Female
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Gene Expression
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Genetic Loci*
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Genome-Wide Association Study
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Humans
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Imidazoline Receptors / genetics
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Imidazoline Receptors / metabolism
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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MDS1 and EVI1 Complex Locus Protein / genetics
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MDS1 and EVI1 Complex Locus Protein / metabolism
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Male
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Mice
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Otitis Media with Effusion / genetics*
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Otitis Media with Effusion / metabolism
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Otitis Media with Effusion / pathology
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Protein-Arginine N-Methyltransferases / genetics*
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Protein-Arginine N-Methyltransferases / metabolism
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Signal Transduction
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Transforming Growth Factor beta1 / genetics*
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Transforming Growth Factor beta1 / metabolism
Substances
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F-Box Proteins
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Homeodomain Proteins
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Imidazoline Receptors
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Intracellular Signaling Peptides and Proteins
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MDS1 and EVI1 Complex Locus Protein
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MECOM protein, human
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NISCH protein, human
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Repressor Proteins
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TGFB1 protein, human
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TGIF1 protein, human
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Transforming Growth Factor beta1
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FBXO11 protein, human
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Protein-Arginine N-Methyltransferases