Laboratory of Immunology, EPS Charles Nicolle, Tunis, Tunisia.
Digestion. 2011;83(4):269-74. doi: 10.1159/000319755. Epub 2011 Jan 28.
Interleukin (IL)-18 can regulate the Th2-mediated immune response and it may be involved in the pathogenesis of Th1 and Th2 chronic inflammatory diseases. This study sought to detect a possible association between two single nucleotide polymorphisms (SNPs) (-137G/C and -607C/A) in the IL-18 gene promoter region and susceptibility to inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population.
The (-137G/C and -607C/A) IL-18 polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the sequence-specific polymerase chain reaction method.
The distribution of allele and genotype frequencies illustrate that the -137G/G genotype frequency was significantly higher in UC than in controls (p value corrected (pc) = 0.038). On the other hand, we found a statistically significant association (pc = 0.033) between genotype AA of the IL-18 gene promoter (-607C/A) polymorphism in UC patients and the distal localization of the lesions. In CD, no significant differences were observed at positions -607 and -137. The analysis of IBD patients according to clinical behavior revealed no difference.
The two SNPs at position -607 (C/A) and -137 (G/C) in the promoter region of the IL-18 gene was associated with the development of UC but not CD, providing a strong support for an IBD susceptibility gene in the region surrounding IL-18. It remains to be determined precisely how the IL-18 alleles influence the pathogenesis of IBD.
白细胞介素(IL)-18 可调节 Th2 介导的免疫反应,可能参与 Th1 和 Th2 慢性炎症性疾病的发病机制。本研究旨在检测白细胞介素-18 基因启动子区域两个单核苷酸多态性(SNP)(-137G/C 和-607C/A)与炎症性肠病(IBD)包括克罗恩病(CD)和溃疡性结肠炎(UC)易感性之间的可能关联。
采用序列特异性聚合酶链反应方法分析了 105 例 CD 患者、59 例 UC 患者和 100 名对照者中 IL-18 基因的-137G/C 和-607C/A 多态性。
等位基因和基因型频率分布表明,UC 患者-137G/G 基因型频率明显高于对照组(校正 p 值(pc)=0.038)。另一方面,我们发现 UC 患者 IL-18 基因启动子-607(C/A)多态性 AA 基因型与病变的远端定位之间存在统计学显著相关性(pc=0.033)。在 CD 中,-607 和-137 位无明显差异。根据临床行为对 IBD 患者进行分析,无差异。
IL-18 基因启动子区-607(C/A)和-137(G/C)两个 SNP 与 UC 的发生有关,而与 CD 无关,为 IL-18 周围区域存在 IBD 易感基因提供了有力支持。尚需确定 IL-18 等位基因如何影响 IBD 的发病机制。