Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Pediatric Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
J Clin Lab Anal. 2019 May;33(4):e22835. doi: 10.1002/jcla.22835. Epub 2019 Feb 1.
Fork head/winged helix transcription factor (Foxp3) plays a pivotal role in regulatory T (Treg) cells. The present study aimed to assess the association of Crohn's disease (CD) with Foxp3 polymorphisms and its colonic expression in Chinese patients.
The Foxp3 polymorphisms, rs3761547, rs2232365, rs2294021, and rs3761548, were examined by SNaPshot in 268 CD patients and 490 controls. The colonic expression levels of Foxp3, IL-2, and IL-4 were detected in 31 CD patients and 31 controls using real-time quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay.
Compared to male controls, the proportion of variant allele of rs3761547 was increased in male patients. The variant alleles of rs3761547, rs2232365, and rs2294021 were less in male patients with stricturing CD compared to those with non-stricturing, non-penetrating CD; however, these variants were frequently detected in male patients with colonic CD than in those with ileocolonic CD. The variant allele of rs3761548 was increased in male patients with penetrating CD compared to those with non-stricturing, non-penetrating CD. The colonic expression of Foxp3 was higher in CD patients than in controls (both males and females). Compared to male patients carrying wild-type alleles, the colonic expression of Foxp3 was downregulated in male patients with variant alleles, rs3761547, rs2232365, rs2294021, and rs3761548, respectively. However, the Foxp3 polymorphisms were not significantly related with the colonic expression levels of IL-2 and IL-4 in CD patients (both males and females).
Foxp3 polymorphisms might increase the CD susceptibility by reducing the colonic expression of Foxp3 in male patients.
叉头/翅膀状螺旋转录因子（Foxp3）在调节性 T（Treg）细胞中发挥关键作用。本研究旨在评估 Foxp3 多态性与中国患者克罗恩病（CD）的相关性及其在结肠中的表达。
采用 SNaPshot 检测 268 例 CD 患者和 490 例对照者 Foxp3 多态性 rs3761547、rs2232365、rs2294021 和 rs3761548。采用实时定量聚合酶链反应、免疫组织化学和酶联免疫吸附试验检测 31 例 CD 患者和 31 例对照者 Foxp3、IL-2 和 IL-4 的结肠表达水平。
与男性对照者相比，男性患者 rs3761547 变异等位基因的比例增加。与非狭窄非穿透性 CD 患者相比，狭窄性 CD 男性患者 rs3761547、rs2232365 和 rs2294021 的变异等位基因较少；然而，这些变体在结肠 CD 男性患者中比在回结肠 CD 患者中更为常见。穿透性 CD 男性患者 rs3761548 变异等位基因的比例高于非狭窄非穿透性 CD 患者。CD 患者结肠 Foxp3 的表达高于对照组（男性和女性）。与携带野生型等位基因的男性患者相比，Foxp3 的结肠表达在分别携带 rs3761547、rs2232365、rs2294021 和 rs3761548 变异等位基因的男性患者中下调。然而，Foxp3 多态性与 CD 患者（男性和女性）结肠中 IL-2 和 IL-4 的表达水平无显著相关性。
Foxp3 多态性可能通过降低男性患者结肠中 Foxp3 的表达，增加 CD 的易感性。
