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Updated: May 26, 2025
Diagnosis of Hirschsprung's Disease by Immunostaining Rectal Suction Biopsies for Calretinin, S100 Protein and Protein Gene Product 9.5
Published on: April 26, 2019
Hirschsprung's disease may increase the incidence of inflammatory bowel disease through alterations in CA1
Insights
Hirschsprung's disease (HSCR) increases the risk of developing inflammatory bowel disease (IBD). Lower CA1 gene expression in IBD patients suggests it may be a therapeutic target for HSCR complicated with IBD.
Area of Science:
- Genetics and Molecular Biology
- Gastroenterology
- Disease Pathogenesis
Background:
- The relationship between Hirschsprung's disease (HSCR) and inflammatory bowel disease (IBD) is not well understood.
- Common pathogenic mechanisms underlying HSCR and IBD require further investigation.
Purpose of the Study:
- To investigate the potential causal relationship between HSCR and IBD.
- To explore the shared pathogenesis and identify potential therapeutic targets.
Main Methods:
- Mendelian randomization analysis was performed to assess causality.
- Differentially expressed genes (DEGs) in HSCR and IBD tissues were identified.
- Pathway enrichment analysis and molecular docking were utilized to explore mechanisms and drug targets.
Main Results:
- HSCR was associated with an increased risk of developing IBD (OR = 1.048, P < 0.05).
- 111 DEGs in IBD and 471 DEGs in HSCR were identified.
- CA1 was identified as a core gene with lower expression in IBD and inflamed tissues, linked to TNF and IL17 signaling pathways.
Conclusions:
- HSCR promotes the occurrence of IBD, revealing underlying pathogenesis.
- Reduced CA1 expression in IBD suggests its potential as a therapeutic target for HSCR-associated IBD.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Impact:
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.
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