Association of Crohn's disease with Foxp3 gene polymorphisms and its colonic expression in Chinese patients

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Foxp3 polymorphisms might increase the CD susceptibility by reducing the colonic expression of Foxp3 in male patients.