Association of polymorphisms in the interleukin-18 gene in patients with Crohn's disease depending on the CARD15/NOD2 genotype
Association of polymorphisms in the interleukin-18 gene in patients with Crohn's disease depending on the CARD15/NOD2 genotype
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DOI：
10.1097/01.mib.0000187574.41290.b1
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发表时间：
2005-12-01
影响因子：
4.9
通讯作者：
Folwaczny, C
中科院分区：
文献类型：
--
作者：
Glas, J;Török, HP;Folwaczny, C
背景：白细胞介素18(IL-18)是一种促炎症细胞因子，可诱导IL-γ在克罗恩病(CD)中的表达增加。在IL-18基因中，已知有几个部分功能相关的多态性。方法：采用聚合酶链式反应和限制性片段长度多态性分析方法，对210例CD患者、140例溃疡性结肠炎患者和265例健康对照的IL-18基因-607、-137和密码子35第三位(C35/3)进行基因分型。结果：CD组和溃疡性结肠炎组的IL-18基因-607、-137和密码子35第三位点(c35/3)基因频率、单倍型和二倍型频率与正常对照组比较差异均无统计学意义。在对CD患者进行CARD15/NOD2状态分层后，发现携带CARD15/NOD2突变的CD患者与-137CC(P=0.018)和C35/3CC(P=0.010)以及二倍型2-2(P 0.018)显著相关。仅在CARD15/NOD2基因突变阳性的患者中，-137GG(P=0.015)和C35/3AA型(P=0.030)与结肠病有关，而在CARD15/NOD2基因突变阴性的患者中，-607AA型(P=0.007)与肠瘘相关。结论：在本研究中，CD患者IL-18基因的几种基因型和二倍型存在显著差异。在CD中IL-18表达增加的背景下，IL-18的表达是否受CARD15/NOD2突变状态的影响尚不清楚。
Background: An increased expression of interleukin-18 (IL-18), a proinflammatory cytokine inducing interteron-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 C,CARD15/NOD2 mutation status and clinical phenotypes.Methods: 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.Results: 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.Conclusions: 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.