Hirschsprung's disease may increase the incidence of inflammatory bowel disease through alterations in CA1.

Abstract

The role of Hirschsprung's disease (HSCR) for the development of inflammatory bowel disease (IBD) and the common pathogenesis of the diseases remains unclear. The objective is to investigate the relationship between HSCR and IBD. In our study, the Mendelian randomization approach was employed to analyze the causal relationships. A further search was conducted for differentially expressed genes (DEGs) between disease and control tissues in HSCR and IBD. Subsequently, the potential pathway mechanisms were subjected to an enrichment analysis. Furthermore, the molecular docking was employed to investigate the binding relationship between potential therapeutic targets and drugs. The results show HSCR have an increased risk of developing IBD (IVW: OR = 1.048, P < 0.05; weighted median: OR = 1.065, P < 0.05). A total of 111 DEGs were identified in IBD, while 471 DEGs were observed in HSCR. CA1 was identified as core gene and exhibited lower expression levels in IBD (P < 0.05). Concomitantly, CA1 exhibited reduced expression levels in inflamed tissues. And the TNF and IL17 signaling pathway were found closely related to CA1 expression. In total, our study shows HSCR promote the occurrence of IBD and reveals pathogenesis. Our results suggest CA1 may provide novel insight for the treatment of HSCR complicated with IBD. Individuals with HSCR are at a higher risk of developing IBD (IVW: OR = 1.048, P < 0.05; Weighted median: OR = 1.065, P < 0.05). Patients with IBD exhibited lower expression levels of CA1 (P < 0.05). Furthermore, CA1 expression was found to be lower in inflamed tissues (P < 0.05). CA1 may provide novel insight for the treatment of HSCR complicated with IBD.