Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.
Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.
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DOI：
10.1038/ng.203
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发表时间：
2008-10
期刊：
影响因子：
30.8
通讯作者：
Hakonarson, Hakon
中科院分区：
文献类型：
--
作者：
Kugathasan, Subra;Baldassano, Robert N.;Bradfield, Jonathan P.;Sleiman, Patrick M. A.;Imielinski, Marcin;Guthery, Stephen L.;Cucchiara, Salvatore;Kim, Cecilia E.;Frackelton, Edward C.;Annaiah, Kiran;Glessner, Joseph T.;Santa, Erin;Willson, Tara;Eckert, Andrew W.;Bonkowski, Erin;Shaner, Julie L.;Smith, Ryan M.;Otieno, F. George;Peterson, Nicholas;Abrams, Debra J.;Chiavacci, Rosetta M.;Grundmeier, Robert;Mamula, Petar;Tomer, Gitit;Piccoli, David A.;Monos, Dimitri S.;Annese, Vito;Denson, Lee A.;Grant, Struan F. A.;Hakonarson, Hakon
炎症性肠病（IBD）是一种常见的炎症性疾病，病因复杂，涉及遗传和环境诱因，包括但不限于细菌清除缺陷、黏膜屏障缺陷以及对肠道共生菌免疫反应的持续失调。IBD具有两种不同的表型：克罗恩病（CD）和溃疡性结肠炎（UC）。先前报道的全基因组关联研究（GWA）已经确定了遗传变异，这些变异在CD总体遗传易感性中占一小部分，对UC发病机制的贡献更小。我们假设根据发病年龄对IBD进行分层可能会识别出与IBD相关的其他基因。为此，我们在一组1011例儿童期发病的IBD患者和4250例匹配的对照中进行了全基因组关联分析。我们在20号染色体长臂13区（20q13）（rs2315008[T]和rs4809330[A]；分别为P = 6.30×10⁻⁸和6.95×10⁻⁸；两者的优势比（OR）均为0.74）以及21号染色体长臂22区（21q22）（rs2836878[A]；P = 6.01×10⁻⁸；OR = 0.73）上识别并复制出了显著相关且先前未报道的基因位点，它们分别靠近肿瘤坏死因子受体超家族成员6B（TNFRSF6B）基因和蛋白酶体组装伴侣1（PSMG1）基因。
Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn’s disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 × 10−8 and 6.95 × 10−8, respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 × 10−8; OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.
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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：
168.9
作者：
Satsangi, J;Welsh, KI;Jewell, DP
通讯作者：
Jewell, DP
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.