A NFKB1 promoter polymorphism is involved in susceptibility to ulcerative colitis
A NFKB1 promoter polymorphism is involved in susceptibility to ulcerative colitis
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DOI：
10.1111/j.1744-313x.2005.00546.x
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发表时间：
2005-12-01
影响因子：
2.2
通讯作者：
Bouma, G
中科院分区：
文献类型：
--
作者：
Borm, MEA;van Bodegraven, AA;Bouma, G
核因子-κ B（NF-κ B）是一组参与多种免疫和/或炎症过程的关键转录因子。可以想象，参与NF-κ B通路的基因是慢性炎症性疾病的感兴趣的候选基因，包括炎症性肠病（IBD）、克罗恩病（CD）和溃疡性结肠炎（UC）。在两种结肠炎小鼠模型中，观察到与3号染色体上含有Nfkb 1基因的基因座的强烈连锁。此外，人类NFKB 1基因启动子区的多态性被发现与UC的易感性相关。在这项研究中，我们在不同人群中进行了搜索，以确认先前发现的IBD相关性。在266名无关的荷兰白人IBD患者（127名UC，139名CD）和155名匹配的健康对照中测定了-94 ins/delATTG多态性的等位基因和基因型频率。与健康对照组相比，UC患者中该缺失的等位基因频率显著较高（P = 0.019），但CD患者中并非如此，并且-94 ATTG缺失纯合子的UC患者的发病年龄更小。我们的研究结果证实了先前在独立研究人群中发现的该多态性与UC易感性之间的关联，并为该基因在疾病易感性中的作用提供了进一步的证据。
Nuclear factor kappa B (NF-kappa B) designates a group of critical transcription factors involved in a variety of immunologic and/or inflammatory processes. Conceivably, genes involved in the NF-kappa B pathway make interesting candidate genes for chronic inflammatory disorders, including the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC). In two mouse models of colitis, strong linkage has been observed with a locus on chromosome 3 that harbours the Nfkb1 gene. In addition, a polymorphism in the promoter region of the human NFKB1 gene was found to be associated with susceptibility to UC. In this study, we searched to confirm this previously found association in IBD in a different population. Allele and genotype frequencies of the -94 ins/delATTG polymorphism were determined in 266 unrelated Dutch Caucasian IBD patients (127 UC, 139 CD), and 155 matched healthy controls. The allele frequency of the deletion was significantly higher in UC patients (P = 0.019), but not in CD patients, compared to healthy controls, and the UC patients homozygous for the -94 ATTG deletion had a younger age of onset. Our findings confirm the previously found association between this polymorphism and susceptibility to UC in an independent study population and adds further evidence for the role of this gene in disease susceptibility.