FXR Activation and Genetic Variation in Inflammatory Bowel Disease
Author Information
Author(s): Nijmeijer Rian M., Gadaleta Raffaella M., van Mil Saskia W. C., van Bodegraven Adriaan A., Crusius J. Bart A., Dijkstra Gerard, Hommes Daan W., de Jong Dirk J., Stokkers Pieter C. F., Verspaget Hein W., Weersma Rinse K., van der Woude C. Janneke, Stapelbroek Janneke M., Schipper Marguerite E. I., Wijmenga Cisca, van Erpecum Karel J., Oldenburg Bas
Primary Institution: University Medical Center Utrecht
Hypothesis
Is FXR activation repressed in the ileum and colon of inflammatory bowel disease patients in remission, and is genetic variation in FXR associated with IBD?
Conclusion
FXR activation in the ileum is decreased in patients with Crohn's colitis, potentially due to altered bile salt circulation or inflammatory signals, but not due to the studied genetic variations.
Supporting Evidence
- mRNA expression of SHP was 50% lower in Crohn's colitis patients compared to controls.
- No SNPs were significantly associated with IBD after correction for multiple testing.
- Ileal FXR expression was unchanged, but SHP expression was reduced in Crohn's patients.
Takeaway
This study found that a protein called FXR, which helps control inflammation in the gut, doesn't work as well in people with Crohn's disease, but the genes studied didn't seem to cause this problem.
Methodology
mRNA expression of FXR and its target gene SHP was measured in biopsies from IBD patients and healthy controls, and genetic variations in FXR were analyzed in a large cohort.
Potential Biases
Potential type II error due to low prevalence of some SNPs.
Limitations
The study did not find significant associations after correcting for multiple testing, and some SNP assays failed.
Participant Demographics
Patients included 1162 with Crohn's disease and 1193 with ulcerative colitis, along with 853 healthy controls.
Statistical Information
P-Value
0.039
Confidence Interval
95% CI 1.02–1.71
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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