Association Between Il‐18 Gene Promoter Polymorphisms and Inflammatory Bowel Disease in a Japanese Population
Association Between Il‐18 Gene Promoter Polymorphisms and Inflammatory Bowel Disease in a Japanese Population
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DOI：
10.1097/01.mib.0000182868.67025.b9
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发表时间：
2005-12
影响因子：
4.9
通讯作者：
T. Takagawa;K. Tamura;N. Takeda;T. Tomita;Y. Ohda;K. Fukunaga;N. Hida;K. Ohnishi;K. Hori;T. Kosaka;Y. Fukuda;H. Ikeuchi;T. Yamamura;H. Miwa;T. Matsumoto
中科院分区：
文献类型：
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作者：
T. Takagawa;K. Tamura;N. Takeda;T. Tomita;Y. Ohda;K. Fukunaga;N. Hida;K. Ohnishi;K. Hori;T. Kosaka;Y. Fukuda;H. Ikeuchi;T. Yamamura;H. Miwa;T. Matsumoto
背景：白细胞介素-18 (IL-18) 是一种多效细胞因子，可诱导干扰素 (IFN) 的产生，并调节 Th2 细胞因子。最近，报道了 IL-18 基因启动子多态性与几种 Th1 或 Th2 介导的炎症性疾病之间的关联研究。在炎症性肠病 (IBD) 中，包括溃疡性结肠炎 (UC) 和克罗恩病 (CD)，最近的证据表明 IL-18 参与了发病机制。方法：利用DNA直接测序，我们研究了IL-18基因启动子在-607C/A和-137G/C处的多态性。对 210 名日本 UC 患者、205 名 CD 患者和 212 名对照患者的等位基因、基因型和单倍型频率进行了测定。结果：在 UC 中，直肠炎型患者的 -137C 等位基因频率显着高于对照组（Pc = 0.0068）。直肠炎型患者的−137 基因型频率也与对照组显着不同（Pc = 0.032）。 Bonferroni 校正后，没有其他等位基因和基因型频率与 UC 显着相关。此外，单倍型 2 (−607A、−137C) 的频率比之前报道的其他单倍型更低，其启动子活性和 IFN-mRNA 水平在直肠炎型患者中显着高于对照组 (Pc = 0.01)。在CD中，我们找不到任何显着差异。结论：IL-18基因启动子多态性可能与UC的疾病易感性无关，但与疾病程度有关。
Background: Interleukin‐18 (IL‐18) is a pleiotropic cytokine that induces the production of interferon (IFN)‐ and also to regulate Th2 cytokines. Recently, association studies between IL‐18 gene promoter polymorphisms and several Th1‐ or Th2‐mediated inflammatory diseases were reported. In inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), recent evidence suggests that IL‐18 is involved in the pathogenesis. Methods: Using DNA direct sequencing, we investigated IL‐18 gene promoter polymorphisms at −607C/A and −137G/C. Allele, genotype, and haplotype frequencies were determined in 210 Japanese patients with UC, 205 patients with CD, and 212 controls. Results: In UC, the −137C allele frequency was significantly higher in the proctitis‐type patients than in controls (Pc = 0.0068). The −137 genotype frequency was also significantly different in the proctitis‐type patients than in controls (Pc = 0.032). No other allele and genotype frequencies were significantly associated with UC after Bonferroni correction. Furthermore, the frequency of haplotype 2 (−607A, −137C), which had a lower promoter activity and IFN‐ mRNA level than the other haplotypes as previously reported, was significantly higher in the proctitis‐type patients than in controls (Pc = 0.01). In CD, we could not find any significant differences. Conclusions: IL‐18 gene promoter polymorphisms may not be associated with disease susceptibility but related to the extent of disease in UC.