Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Life Sci. 2012 May 22;90(19-20):740-6. doi: 10.1016/j.lfs.2012.03.017. Epub 2012 Mar 27.
Although polymorphisms in IL23R have recently been proposed to predispose to Behcet's disease (BD), associations between IL23R polymorphisms and intestinal BD have yet to be elucidated. We therefore performed a study to evaluate whether IL17A, IL23R, and STAT4 polymorphisms are associated with susceptibility to intestinal BD in the Korean population.
Single nucleotide polymorphisms (SNP) in the IL17A, IL23R, and STAT4 genes were analyzed using DNA sequencing, denaturing high performance liquid chromatography, and TaqMan genotyping assays.
Individual polymorphism analysis revealed that the TT genotype of IL17A rs8193036 (odds ratio (OR) 2.10, 95% confidence interval (CI) (1.12-3.92), p=0.021), and GG+GT genotype of IL23R rs1884444 (OR 1.92, 95% CI (1.03-3.57), p=0.034) was associated with the development of intestinal BD. When these two genotypes were combined, the risk of BD increased compared to that of patients with no-risk or one-risk genotype (OR 2.21, 95% CI (1.13-4.34), p=0.021). Furthermore, statistically significant gene-gene interactions were observed between G149R in IL23R vs. rs11685878 in STAT4, rs2275913 in IL17A vs. rs7574865 in STAT4, and rs11889341 in STAT4 vs. rs2275913 in IL17A. The haplotypes of IL17A had a positive association with intestinal BD risks, whereas those of IL23R were protective for disease development.
Our results indicate that the interaction of specific IL17A, IL23R, and STAT4 SNPs modulate susceptibility to intestinal BD in the Korean population, suggesting that the IL-17/23 axis plays a significant role in disease pathogenesis.
尽管 IL23R 中的多态性最近被提出易患白塞病（BD），但 IL23R 多态性与肠 BD 之间的关联尚未阐明。因此，我们进行了一项研究，以评估 IL17A、IL23R 和 STAT4 多态性是否与韩国人群的肠 BD 易感性相关。
使用 DNA 测序、变性高效液相色谱和 TaqMan 基因分型检测分析 IL17A、IL23R 和 STAT4 基因中的单核苷酸多态性（SNP）。
个体多态性分析显示，IL17A rs8193036 的 TT 基因型（比值比（OR）2.10，95%置信区间（CI）（1.12-3.92），p=0.021）和 IL23R rs1884444 的 GG+GT 基因型（OR 1.92，95% CI（1.03-3.57），p=0.034）与肠 BD 的发生相关。当将这两种基因型组合时，与无风险或一种风险基因型的患者相比，BD 的风险增加（OR 2.21，95% CI（1.13-4.34），p=0.021）。此外，还观察到 IL23R 中的 G149R 与 STAT4 中的 rs11685878、IL17A 中的 rs2275913 与 STAT4 中的 rs7574865 以及 STAT4 中的 rs11889341 与 IL17A 中的 rs2275913 之间存在统计学显著的基因-基因相互作用。IL17A 的单体型与肠 BD 风险呈正相关，而 IL23R 的单体型对疾病发展具有保护作用。
我们的结果表明，特定的 IL17A、IL23R 和 STAT4 SNP 的相互作用调节了韩国人群肠 BD 的易感性，表明 IL-17/23 轴在疾病发病机制中起重要作用。
