A mouse-to-man candidate gene study identifies association of chronic otitis media with the loci TGIF1 and FBXO11.
A mouse-to-man candidate gene study identifies association of chronic otitis media with the loci TGIF1 and FBXO11.
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DOI：
10.1038/s41598-017-12784-8
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发表时间：
2017-10-02
影响因子：
4.6
通讯作者：
Burton MJ
中科院分区：
文献类型：
--
作者：
Bhutta MF;Lambie J;Hobson L;Goel A;Hafrén L;Einarsdottir E;Mattila PS;Farrall M;Brown S;Burton MJ
慢性渗出性中耳炎是儿童听力损失的最常见原因，已知具有很高的遗传性。突变的小鼠模型已经确定Fbxo11、Evi1、Tgif1和Nisch是潜在的危险基因座。我们招募了来自英国35家医院的10岁及以下接受手术治疗的儿童及其核心家庭。我们进行了与FBXO11、EVI1、TGIF1和NISCH基因座的关联测试，并试图在来自芬兰的病例对照队列中复制有意义的结果。检测了1 296个家系(3828个个体)，发现T等位基因与rs881835(p = 0.006，OR1.39)、G等位基因(p = 0.007，OR1.58)、A等位基因(rs10490302，p = 0.016，OR1.17)和G等位基因(p = 0.038，OR1.16)有关联。结果没有被复制。这项研究支持一些较小规模的研究，这些研究也表明中耳炎与FBX011基因的多态性有关，但这是第一个报告与TGIF1基因座相关的研究。FBX011和TGIF1都参与了转化生长因子-β信号转导，提示这一途径在中耳炎症从急性向慢性的转变过程中可能是重要的，并可能成为一个潜在的分子靶点。
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.
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Nischarin的突变通过LIMK1和NF-κB途径引起中耳炎。
影响因子：
4.5
作者：
Crompton M;Purnell T;Tyrer HE;Parker A;Ball G;Hardisty-Hughes RE;Gale R;Williams D;Dean CH;Simon MM;Mallon AM;Wells S;Bhutta MF;Burton MJ;Tateossian H;Brown SDM
通讯作者：
Brown SDM
影响因子：
1.9
作者：
Bhutta, Mahmood F.;Hobson, Lindsey;Furniss, Dominic
通讯作者：
Furniss, Dominic
DOI：
10.1016/j.bbrc.2015.07.037
发表时间：
2015-09-04
影响因子：
3.1
作者：
Ju, Uk-Il;Park, Jong-Wan;Chun, Yang-Sook
通讯作者：
Chun, Yang-Sook
影响因子：
4.6
作者：
Einarsdottir E;Hafrén L;Leinonen E;Bhutta MF;Kentala E;Kere J;Mattila PS
通讯作者：
Mattila PS
影响因子：
4.5
作者：
Cheeseman MT;Tyrer HE;Williams D;Hough TA;Pathak P;Romero MR;Hilton H;Bali S;Parker A;Vizor L;Purnell T;Vowell K;Wells S;Bhutta MF;Potter PK;Brown SD
通讯作者：
Brown SD