Common variants in the NLRP3 region contribute to Crohn's disease susceptibility.
Common variants in the NLRP3 region contribute to Crohn's disease susceptibility.
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DOI：
10.1038/ng.285
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发表时间：
2009-01
期刊：
影响因子：
30.8
通讯作者：
Franchimont, Denis
中科院分区：
文献类型：
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作者：
Villani, Alexandra-Chloe;Lemire, Mathieu;Fortin, Genevieve;Louis, Edouard;Silverberg, Mark S.;Collette, Catherine;Baba, Nobuyasu;Libioulle, Cecile;Belaiche, Jacques;Bitton, Alain;Gaudet, Daniel;Cohen, Albert;Langelier, Diane;Fortin, Paul R.;Wither, Joan E.;Sarfati, Marika;Rutgeerts, Paul;Rioux, John D.;Vermeire, Severine;Hudson, Thomas J.;Franchimont, Denis
我们使用候选基因的方法来确定一组SNP，位于NLRP 3（以前称为CIAS 1和NALP 3）下游染色体1 q44上的预测调控区，与克罗恩病相关。该协会一直复制在四个样本集的欧洲血统的个人。在所有样本的综合分析中（710例父-母-子三人组，239例病例和107例对照），这些SNPs与克罗恩病的风险密切相关（对于rs 10733113，P合并= 3.49 × 10−9，比值比= 1.78，置信区间= 1.47-2.16），达到与全基因组关联研究所规定的严格显著性阈值一致的水平。此外，我们观察到相关区域的SNP与NLRP 3表达和IL-1β产生之间存在显著相关性。已知NLRP 3突变导致三种罕见的自身炎症性疾病。这些结果表明，NLRP 3区域也与更常见的炎性疾病如克罗恩病的易感性有关。
We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3), that are associated with Crohn's disease. The associations were consistently replicated in four sample sets from individuals of European descent. In the combined analysis of all samples (710 father-mother-child trios, 239 cases and 107 controls), these SNPs were strongly associated with risk of Crohn's disease (Pcombined = 3.49 × 10−9, odds ratio = 1.78, confidence interval = 1.47–2.16 for rs10733113), reaching a level consistent with the stringent significance thresholds imposed by whole-genome association studies. In addition, we observed significant associations between SNPs in the associated regions and NLRP3 expression and IL-1β production. Mutations in NLRP3 are known to be responsible for three rare autoinflammatory disorders. These results suggest that the NLRP3 region is also implicated in the susceptibility of more common inflammatory diseases such as Crohn's disease.
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DOI：
10.1073/pnas.88.16.7276
发表时间：
1991-08-01
影响因子：
11.1
作者：
HOLLAND, PM;ABRAMSON, RD;GELFAND, DH
通讯作者：
GELFAND, DH
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：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.