Department of Gastroenterology, Kanazawa Medical University, 1-1, Daigaku, Uchinada-machi, Ishikawa, 920-0293, Japan.
Clin Exp Med. 2013 Nov;13(4):239-44. doi: 10.1007/s10238-012-0206-5. Epub 2012 Sep 7.
Interleukin-17A plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We investigated the association between ulcerative colitis (UC) and polymorphisms of IL17A, rs2275913 (-197 G > A), and rs3748067 (*1249 C > T). The study was performed in 475 healthy subjects (controls) and 202 with UC (UC cases), including 113 controls and 64 UC cases from previous study. We employed the multiplex PCR-SSCP method to detect gene polymorphisms. The minor allele frequency of rs2275913 was significantly higher but that of rs3748067 was significantly lower in UC cases than controls. The rs2275913 minor homozygote (AA) had an increased risk of the development of UC, whereas rs3748067 minor carrier (CT + TT) had decreased risks for the development of UC. When compared with LR group (rs2275913 GG + GA with rs3748067 CT + TT), HR group (rs2275913 AA with rs3748067 CC) had a more increased risk of the development of UC (OR, 3.38; p = 0.0007). The polymorphisms of IL17A were associated with the noncontinuous and pancolitis phenotypes of UC. Our results suggest that IL17A polymorphisms (both rs2275913 and rs3748067) influence the susceptibility to and pathophysiological features of UC, coordinately.
白细胞介素-17A 通过诱导促炎细胞因子和中性粒细胞趋化因子的释放,在组织炎症中发挥作用。我们研究了溃疡性结肠炎 (UC) 与白细胞介素-17A 的 rs2275913(-197 G > A) 和 rs3748067(*1249 C > T) 多态性之间的关联。该研究在 475 名健康受试者(对照组)和 202 名 UC 患者(UC 病例)中进行,其中包括来自先前研究的 113 名对照组和 64 名 UC 病例。我们采用多重 PCR-SSCP 方法检测基因多态性。与对照组相比,UC 病例中 rs2275913 的次要等位基因频率显著升高,而 rs3748067 的频率显著降低。rs2275913 次要纯合子(AA)发生 UC 的风险增加,而 rs3748067 携带较小等位基因(CT + TT)发生 UC 的风险降低。与 LR 组(rs2275913 GG + GA 与 rs3748067 CT + TT)相比,HR 组(rs2275913 AA 与 rs3748067 CC)发生 UC 的风险增加更明显(OR,3.38;p = 0.0007)。白细胞介素-17A 多态性与 UC 的非连续性和全结肠炎表型有关。我们的结果表明,白细胞介素-17A 多态性(rs2275913 和 rs3748067)共同影响 UC 的易感性和病理生理特征。