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

doi:10.1186/s13148-024-01631-z

. 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 Belot³, Xiaojian Shao⁴, Christophe Penna¹, Antoine Brouquet¹, Pierre Bougnères^{5

6

7}

Affiliations

¹ Department of Visceral and Digestive Surgery, Hôpital Bicêtre AP-HP, Paris Saclay University, 94276, Le Kremlin-Bicêtre Cedex, France.
² UMR INSERM 1169 and Université Paris Saclay, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France.
³ Groupe d'Études sur le Diabète, l'Obésité, la Croissance, GETDOC, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France.
⁴ Digital Technologies Research Center, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
⁵ UMR INSERM 1169 and Université Paris Saclay, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France. pierre@bougneres.fr.
⁶ Groupe d'Études sur le Diabète, l'Obésité, la Croissance, GETDOC, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France. pierre@bougneres.fr.
⁷ MIRCEN Institute, CEA Paris-Saclay/site de Fontenay-aux-Roses, Bâtiment 56 PC 103, 18 route du Panorama, BP6 92265, Fontenay-aux-Roses Cedex, France. pierre@bougneres.fr.

^# Contributed equally.

PMID: 38355645
PMCID: PMC10865720
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 et al. Clin Epigenetics. 2024.

. 2024 Feb 14;16(1):28.

doi: 10.1186/s13148-024-01631-z.

Authors

Charles de Ponthaud^#^{1

2}, Solafah Abdalla^#^{1

2}, Marie-Pierre Belot³, Xiaojian Shao⁴, Christophe Penna¹, Antoine Brouquet¹, Pierre Bougnères^{5

6

7}

Affiliations

¹ Department of Visceral and Digestive Surgery, Hôpital Bicêtre AP-HP, Paris Saclay University, 94276, Le Kremlin-Bicêtre Cedex, France.
² UMR INSERM 1169 and Université Paris Saclay, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France.
³ Groupe d'Études sur le Diabète, l'Obésité, la Croissance, GETDOC, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France.
⁴ Digital Technologies Research Center, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
⁵ UMR INSERM 1169 and Université Paris Saclay, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France. pierre@bougneres.fr.
⁶ Groupe d'Études sur le Diabète, l'Obésité, la Croissance, GETDOC, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France. pierre@bougneres.fr.
⁷ MIRCEN Institute, CEA Paris-Saclay/site de Fontenay-aux-Roses, Bâtiment 56 PC 103, 18 route du Panorama, BP6 92265, Fontenay-aux-Roses Cedex, France. pierre@bougneres.fr.

^# Contributed equally.

PMID: 38355645
PMCID: PMC10865720
DOI: 10.1186/s13148-024-01631-z

Erratum in

Correction: Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease.
de Ponthaud C, Abdalla S, Belot MP, Shao X, Penna C, Brouquet A, Bougnères P. de Ponthaud C, et al. Clin Epigenetics. 2024 Mar 18;16(1):43. doi: 10.1186/s13148-024-01654-6. Clin Epigenetics. 2024. PMID: 38500164 Free PMC article. No abstract available.

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**
Methylation of the 4 CpGs in the 1^st 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

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Correction: Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease.
de Ponthaud C, Abdalla S, Belot MP, Shao X, Penna C, Brouquet A, Bougnères P. de Ponthaud C, et al. Clin Epigenetics. 2024 Mar 18;16(1):43. doi: 10.1186/s13148-024-01654-6. Clin Epigenetics. 2024. PMID: 38500164 Free PMC article. No abstract available.

References

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[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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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

[8] 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

[9] 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

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

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