Brighton and Sussex University Hospitals NHS Trust, Eastern Road, Brighton, BN2 5BE, UK.
Nuffield Department of Surgical Sciences, University of Oxford, Headley Way, Oxford, OX3 9DU, UK.
Sci Rep. 2017 Oct 2;7(1):12496. doi: 10.1038/s41598-017-12784-8.
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.
慢性分泌性中耳炎（COME）是儿童听力损失的最常见原因，且已知其具有较高的遗传性。突变小鼠模型已经确定了 FBXO11、EVI1、TGIF1 和 NISCH 作为潜在的风险基因座。我们从英国的 35 家医院招募了年龄在 10 岁以下正在接受 COME 手术治疗的儿童及其核心家庭。我们对 FBXO11、EVI1、TGIF1 和 NISCH 基因座进行了关联测试，并试图在芬兰的病例对照队列中复制显著结果。我们共检测了 1296 个家庭（3828 个人），发现 rs881835 处的 T 等位基因（p=0.006，OR 1.39）和 rs1962914 处的 G 等位基因（p=0.007，OR 1.58）与 TGIF1 之间存在关联，rs10490302 处的 A 等位基因（p=0.016，OR 1.17）和 rs2537742 处的 G 等位基因（p=0.038，OR 1.16）与 FBXO11 之间存在关联。这些结果没有得到复制。这项研究支持了一些规模较小的研究，这些研究也表明中耳炎与 FBXO11 多态性有关，但这是第一项报道与 TGIF1 基因座有关的研究。FBXO11 和 TGIF1 都参与 TGF-β 信号转导，这表明该途径可能在急性向慢性中耳炎症的转变中起重要作用，是一个潜在的分子靶点。
