MAST3: a novel IBD risk factor that modulates TLR4 signaling.
MAST3: a novel IBD risk factor that modulates TLR4 signaling.
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MAST3：一种调节TLR4信号传导的新型IBD风险因素。
DOI：
10.1038/gene.2008.57
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发表时间：
2008-10
影响因子：
5
通讯作者：
Rioux, J. D.
中科院分区：
文献类型：
--
作者：
Labbe, C.;Goyette, P.;Lefebvre, C.;Stevens, C.;Green, T.;Tello-Ruiz, M. K.;Cao, Z.;Landry, A. L.;Stempak, J.;Annese, V.;Latiano, A.;Brant, S. R.;Duerr, R. H.;Taylor, K. D.;Cho, J. H.;Steinhart, A. H.;Daly, M. J.;Silverberg, M. S.;Xavier, R. J.;Rioux, J. D.
炎症性肠病(IBD)是一种在遗传易感宿主中由多种因素引起的慢性疾病。遗传易感性研究的重大进展突显了先天免疫系统在该病中的重要性。我们之前完成了全基因组连锁研究，并在染色体19p上发现了一个重要的基因座(IBD6)。我们对确定IBD6的因果变异很感兴趣。我们进行了两个阶段的关联图谱研究。在第一阶段，从HapMap数据库中选择了1530个SNPs，对761例IBD患者进行了基因分型。在超过复制阈值的SNP中，26个SNP在754名额外患者中成功进行了基因分型(第二阶段)。位于MAST3基因的一个内含子突变体rs273506在这两个阶段都有关联(合并P=2×10−4)。我们确定了四个MAST3编码变体，包括一个非同义SNP rs8108738，它们与rs273506相关，并与IBD相关。为了测试MAST3是否在感兴趣的细胞中表达，我们进行了表达分析，结果显示MAST3在抗原提呈细胞和淋巴细胞中大量表达。MAST3特异性地降低TLR4依赖的NF-κB活性。我们的发现进一步证明了核因子-κB活性调节因子在炎症性肠病发病机制中发挥的关键作用。
Inflammatory bowel disease (IBD) is a chronic disorder caused by multiple factors in a genetically susceptible host. Significant advances in the study of genetic susceptibility have highlighted the importance of the innate immune system in this disease. We previously completed a genomewide linkage study and found a significant locus (IBD6) on chromosome 19p. We were interested in identifying the causal variant in IBD6. We performed a two-stage association mapping study. In stage one, 1530 SNPs were selected from the HapMap database and genotyped in 761 patients with IBD. Among the SNPs that passed the threshold for replication, 26 were successfully genotyped in 754 additional patients (stage two). One intronic variant, rs273506 located in the MAST3 gene was found to be associated in both stages (pooled P=2×10−4). We identified four MAST3 coding variants, including a non-synonymous SNP rs8108738, correlated to rs273506 and associated to IBD. To test whether MAST3 was expressed in cells of interest, we performed expression assays which showed abundant expression of MAST3 in antigen presenting cells and in lymphocytes. The knockdown of MAST3 specifically decreased TLR4 dependent NF-κB activity. Our findings are additional proof of the pivotal role played by modulators of NF-κB activity in IBD pathogenesis.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Libioulle C;Louis E;Hansoul S;Sandor C;Farnir F;Franchimont D;Vermeire S;Dewit O;de Vos M;Dixon A;Demarche B;Gut I;Heath S;Foglio M;Liang L;Laukens D;Mni M;Zelenika D;Van Gossum A;Rutgeerts P;Belaiche J;Lathrop M;Georges M
通讯作者：
Georges M
影响因子：
30.8
作者：
Hampe, Jochen;Franke, Andre;Schreiber, Stefan
通讯作者：
Schreiber, Stefan
影响因子：
5
作者：
De Jager, P. L.;Franchimont, D.;Rioux, J. D.
通讯作者：
Rioux, J. D.
影响因子：
30.8
作者：
Rioux, JD;Daly, MJ;Hudson, TJ
通讯作者：
Hudson, TJ