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. 2024 Feb 14;16(1):28.
doi: 10.1186/s13148-024-01631-z.

Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease

Charles de Ponthaud #  1   2 , Solafah Abdalla #  1   2 , Marie-Pierre Belot  3 , Xiaojian Shao  4 , Christophe Penna  1 , Antoine Brouquet  1 , Pierre Bougnères  5   6   7
Affiliations

Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease

Charles de Ponthaud et al. Clin Epigenetics. .

Erratum in

Abstract

Background: E-cadherin, a major actor of cell adhesion in the intestinal barrier, is encoded by the CDH1 gene associated with susceptibility to Crohn Disease (CD) and colorectal cancer. Since epigenetic mechanisms are suspected to contribute to the multifactorial pathogenesis of CD, we studied CpG methylation at the CDH1 locus. The methylation of the CpG island (CGI) and of the 1st enhancer, two critical regulatory positions, was quantified in surgical specimens of inflamed ileal mucosa and in peripheral blood mononuclear cells (PBMC) of 21 CD patients. Sixteen patients operated on for a non-inflammatory bowel disease, although not normal controls, provided a macroscopically normal ileal mucosa and PBMC for comparison.

Results: In ileal mucosa, 19/21 (90%) CD patients vs 8/16 control patients (50%) (p < 0.01) had a methylated CDH1 promoter CGI. In PBMC, CD patients with methylated CGI were 11/21 (52%) vs 7/16 controls (44%), respectively. Methylation in the 1st enhancer of CDH1 was also higher in the CD group for each of the studied CpGs and for their average value (45 ± 17% in CD patients vs 36 ± 17% in controls; p < 0.001). Again, methylation was comparable in PBMC. Methylation of CGI and 1st enhancer were not correlated in mucosa or PBMC.

Conclusions: Methylation of several CpGs at the CDH1 locus was increased in the inflamed ileal mucosa, not in the PBMC, of CD patients, suggesting the association of CDH1 methylation with ileal inflammation. Longitudinal studies will explore if this increased methylation is a risk marker for colorectal cancer.

Keywords: CpG methylation; Crohn disease; E-cadherin.

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Conflict of interest statement

P.Bougnères is the scientific founder of Adrenas Therapeutics, which had no role in this research. MPB is an employee of Therapy Design Consulting who gave technical advice to CdP at initiation of the study.

Figures

Fig. 1
Fig. 1
Methylation of the 4 CpGs in the 1st enhancer of CDH1 gene A in mucosa; and B in PBMC B patients with CD or non-inflammatory disease controls. * p 0.03; ** p < 0.02; ***p 0.01
See this image and copyright information in PMC

References

    1. De Souza HSP, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol. 2016;13(1):13–27. doi: 10.1038/nrgastro.2015.186. - DOI - PubMed
    1. Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390(10114):2769–2778. doi: 10.1016/S0140-6736(17)32448-0. - DOI - PubMed
    1. Lee D, Albenberg L, Compher C, Baldassano R, Piccoli D, Lewis JD, et al. Diet in the pathogenesis and treatment of inflammatory bowel diseases. Gastroenterology. 2015;148(6):1087–1106. doi: 10.1053/j.gastro.2015.01.007. - DOI - PMC - PubMed
    1. Manzel A, Muller DN, Hafler DA, Erdman SE, Linker RA, Kleinewietfeld M. Role of “Western Diet” in inflammatory autoimmune diseases. Curr Allergy Asthma Rep. 2014;14(1):404. doi: 10.1007/s11882-013-0404-6. - DOI - PMC - PubMed
    1. Lo CH, Lochhead P, Khalili H, Song M, Tabung FK, Burke KE, et al. Dietary inflammatory potential and risk of Crohn’s disease and ulcerative colitis. Gastroenterology. 2020;159(3):873–883.e1. doi: 10.1053/j.gastro.2020.05.011. - DOI - PMC - PubMed

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