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.
Highlights
IntroductionDiscovery mechanism ENU mutagenesis ENU mutagenesis Knockout ENU mutagenesis
C3H/HeN C3H/HeN C57BL/6J C3H/HeHDiscovery mechanism ENU mutagenesis ENU mutagenesis Knockout ENU mutagenesisReference Hardisty-hughes et al.[9]
We report the largest gene association study to date for OM, where we focus on a cohort of well-phenotyped children with Chronic otitis media with effusion (COME), and we test for association with the four candidate loci identified through mouse models
Summary
Discovery mechanism ENU mutagenesis ENU mutagenesis Knockout ENU mutagenesis. Reference Hardisty-hughes et al.[9] Parkinson et al.[10] Tateossian et al.[28] Crompton[12]. Region(NCBI 36 coordinates) 3:170282244..170349787 2:47882565..47991318 3:52452118..52496071 18:3399072..3451404. Population CEU CEU CEU CEU r2 SNPs force included >0.8 — >0.8 rs2134056, rs330787 >0.8 — >0.8 — Tagging results. The reasons and biology underlying the transition from acute to chronic OM are not known, but epidemiological studies suggest host genetics play a critical role. In a study of twins, Casselbrant reported that time with middle ear effusion in COME had heritability of 71%5. Others have shown that treatment of OM with grommets is associated with a five fold risk of the same treatment in first degree relatives[6]
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