Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship.
Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship.
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溃疡性结肠炎中克罗恩病风险的研究进一步定义了它们的分子关系。
DOI：
10.1053/j.gastro.2008.10.032
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发表时间：
2009-02
期刊：
影响因子：
29.4
通讯作者：
Parkes M
中科院分区：
文献类型：
--
作者：
Anderson CA;Massey DC;Barrett JC;Prescott NJ;Tremelling M;Fisher SA;Gwilliam R;Jacob J;Nimmo ER;Drummond H;Lees CW;Onnie CM;Hanson C;Blaszczyk K;Ravindrarajah R;Hunt S;Varma D;Hammond N;Lewis G;Attlesey H;Watkins N;Ouwehand W;Strachan D;McArdle W;Lewis CM;Wellcome Trust Case Control Consortium;Lobo A;Sanderson J;Jewell DP;Deloukas P;Mansfield JC;Mathew CG;Satsangi J;Parkes M
确定克罗恩病(CD)和溃疡性结肠炎(UC)共有的和疾病特异的易感基因将有助于确定炎症性肠病之间的生物学关系。目前已发现30多个Cd易感基因座。这些都是UC的重要候选易感基因。指数基因组扫描在CD中发现的基因座之前已经测试过与UC的关联，但最近的荟萃分析中发现的那些基因座还在等待这样的调查。此外，最近在ECM1发现的UC基因座需要进行与CD关联的正式测试。我们分析了2527例UC患者和4070例对照人群中的45个单核苷酸多态，标记了最近与CD相关的29个基因座。我们还对1560名CD患者和3028名对照的UC相关ECM1变异体rs11205387进行了基因分型。9个区域显示出与UC相关的29个基因座校正的阈值(P<；.0017)。最强关联(P=4.13×10-8；优势比=1.27)与染色体1q32上包含3个基因的170kb区域相关联。我们还发现了与JAK2的关联，并复制了最近报道的与STAT3的关联，进一步暗示了这一信号通路在炎症性肠病中的作用。其他新的UC易感基因有LYRM4和CDKAL1。其中20个基因座与UC无关，其中几个似乎与CD有关。ECM1变异与CD无关。总的来说，这些数据有助于确定CD和UC之间的遗传关系，并描述共同的和疾病特有的发病机制。
Identifying shared and disease-specific susceptibility loci for Crohn’s disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD. We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls. Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 × 10-8; odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD. Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis.
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影响因子：
7.6
作者：
Rubin, GP;Hungin, APS;Ling, J
通讯作者：
Ling, J
影响因子：
30.8
作者：
Fisher, Sheila A.;Tremelling, Mark;Anderson, Carl A.;Gwilliam, Rhian;Bumpstead, Suzannah;Prescott, Natalie J.;Nimmo, Elaine R.;Massey, Dunecan;Berzuini, Carlo;Johnson, Christopher;Barrett, Jeffrey C.;Cummings, Fraser R.;Drummond, Hazel;Lees, Charlie W.;Onnie, Clive M.;Hanson, Catherine E.;Blaszczyk, Katarzyna;Inouye, Mike;Ewels, Philip;Ravindrarajah, Radhi;Keniry, Andrew;Hunt, Sarah;Carter, Martyn;Watkins, Nick;Ouwehand, Willem;Lewis, Cathryn M.;Cardon, Lon;Lobo, Alan;Forbes, Alastair;Sanderson, Jeremy;Jewell, Derek P.;Mansfield, John C.;Deloukas, Panos;Mathew, Christopher G.;Parkes, Miles;Satsangi, Jack
通讯作者：
Satsangi, Jack
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