Glas Jürgen, Török Helga-Paula, Tonenchi Laurian, Kapser Julia, Schiemann Uwe, Müller-Myhsok Bertram, Folwaczny Matthias, Folwaczny Christian
Medizinische Poliklinik-Innenstadt, Munich, Germany.
Inflamm Bowel Dis. 2005 Dec;11(12):1031-7. doi: 10.1097/01.mib.0000187574.41290.b1.
An increased expression of interleukin-18 (IL-18), a proinflammatory cytokine inducing interferon-gamma, has been found in Crohn's disease (CD). In the IL-18 gene, several partly functional relevant polymorphisms are known. This study sought to investigate associations of IL-18 polymorphisms in inflammatory bowel disease and CD according to CARD15/NOD2 mutation status and clinical phenotypes.
The IL-18 polymorphisms -607, -137, and the third position of codon 35 (c35/3) were genotyped in 210 patients with CD, 140 patients with ulcerative colitis, and 265 healthy controls using polymerase chain reaction and restriction fragment length polymorphism analysis.
Frequencies of alleles and genotypes of the 3 polymorphisms and of the respective haplotypes and diplotypes displayed no significant differences between the whole groups of patients with CD and ulcerative colitis, respectively, compared with the controls. After stratification of patients with CD for CARD15/NOD2 status, significant associations of genotypes -137 CC (P = 0.018) and c35/3 CC (P = 0.010) and of the diplotype 2-2 (P = 0.018) were found in cases carrying CARD15/NOD2 mutations. Associations of genotypes -137 GG (P = 0.015) and c35/3 AA (P = 0.030) with colonic disease only in cases positive for CARD15/NOD2 mutations and of the genotype -607 AA (P = 0.007) with fistulas in cases negative for CARD15/NOD2 mutations were observed.
In this study, significant differences of several genotypes and diplotypes within the IL-18 gene in CD depending on CARD15/NOD2 status have been found. In context with an increased expression of IL-18 in CD, it remains to be shown whether the expression of IL-18 is influenced by CARD15/NOD2 mutation status.
在克罗恩病（CD）中发现促炎细胞因子白细胞介素-18（IL-18）的表达增加，IL-18可诱导γ干扰素。在IL-18基因中，已知有几种部分具有功能相关性的多态性。本研究旨在根据CARD15/NOD2突变状态和临床表型，调查IL-18多态性与炎症性肠病及CD的关联。
采用聚合酶链反应和限制性片段长度多态性分析，对210例CD患者、140例溃疡性结肠炎患者和265名健康对照者的IL-18多态性-607、-137以及密码子35的第3位（c35/3）进行基因分型。
与对照组相比，CD患者组和溃疡性结肠炎患者组整体的3种多态性的等位基因和基因型频率、各自的单倍型和双倍型频率均无显著差异。根据CARD15/NOD2状态对CD患者进行分层后，在携带CARD15/NOD2突变的病例中发现基因型-137 CC（P = 0.018）、c35/3 CC（P = 0.010）以及双倍型2-2（P = 0.018）存在显著关联。仅在CARD15/NOD2突变阳性的病例中观察到基因型-137 GG（P = 0.015）和c35/3 AA（P = 0.030）与结肠疾病的关联，在CARD15/NOD2突变阴性的病例中观察到基因型-6（P = 0.007）与瘘管的关联。
在本研究中，发现CD中IL-18基因内的几种基因型和双倍型根据CARD15/NOD2状态存在显著差异。鉴于CD中IL-18表达增加，IL-18的表达是否受CARD15/NOD2突变状态影响仍有待确定。
