Association between Promotor hypomethylation of TFF1 and Crohn’s Disease

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Sara Hemmati
Golshid Sanati
Mohammad Amin Sadeghi
Naser Ebrahimi Daryani
Nima Rezaei


Inflammatory bowel disease, Crohn disease, Epigenetics, Methylation, Aging


Background and aim: Epigenetic modifications exhibit promising evidence in etiology and prognosis of important diseases such as inflammatory bowel diseases (IBD). In addition to complex factors involved in IBD, a trend toward better prognosis have been reported in older ages of disease onset. Gastrointestinal mucous layer is one of the important components which is disturbed in the disease course. Integrity of this layer is maintained with an anti-inflammatory factor called trefoil factors (TFF). We investigated the methylation status of TFF1 gene in IBD patients alongside with correlation of its alteration level with age of disease onset. Methods: We analyzed the promoter methylation status of TFF1 gene, using the real-time quantitative multiplex methylation specific PCR (QM-MSP). DNA was extracted from colorectal biopsies of 15 Crohn disease cases and 15 healthy controls. Correlation analysis was performed between unmethylated DNA level and age through Pearson correlation coefficient (PPC) test and simple linear regression models. Results:… Our data didn’t provide significant positive correlation of age and TFF1 hypomethylation in Crohn patients (r = .518, p = .058). Conclusions: In conclusion, our case-control study didn’t show significant alteration in TFF1 methylation status in CD patients. (


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1. Ko JK, Auyeung KK. Inflammatory bowel disease: etiology, pathogenesis and current therapy. Current pharmaceutical design. 2014;20(7):1082-96.
2. Yi JM, Kim TO. Epigenetic Alterations in Inflammatory Bowel Disease and Cancer. Intestinal Research. 2015;13(2):112-21.
3. Jung M, Pfeifer GP. Aging and DNA methylation. BMC Biol. 2015;13:7.
4. Duricova D, Burisch J, Jess T, Gower-Rousseau C, Lakatos PL, EpiCom E. Age-related differences in presentation and course of inflammatory bowel disease: an update on the population-based literature. J Crohns Colitis. 2014;8(11):1351-61.
5. Boltin D, Perets TT, Vilkin A, Niv Y. Mucin function in inflammatory bowel disease: an update. Journal of clinical gastroenterology. 2013;47(2):106-11.
6. Thim L, Madsen F, Poulsen SS. Effect of trefoil factors on the viscoelastic properties of mucus gels. Eur J Clin Invest. 2002;32(7):519-27.
7. Buda A, Jepson MA, Pignatelli M. Regulatory function of trefoil peptides (TFF) on intestinal cell junctional complexes. Cell Commun Adhes. 2012;19(5-6):63-8.
8. Song J-Y, Kim B-W, Lee A-W, Lee K-Y, Chung I-S, Lee B-I, et al. Expression of MUC5AC and Trefoil Peptide 1 (TFF1) in the Subtypes of Intestinal Metaplasia. Clinical Endoscopy. 2012;45(2):151-4.
9. Cobler L, Mejias-Luque R, Garrido M, Pera M, Badia-Garrido E, de Bolos C. Activation of the NF-kB pathway downregulates TFF-1 in gastric carcinogenesis. Virchows Arch. 2013;463(4):497-507.
10. Wright NA, Poulsom R, Stamp G, Van Norden S, Sarraf C, Elia G, et al. Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease. Scandinavian journal of gastroenterology Supplement. 1992;193:76-82.
11. Aamann L, Vestergaard EM, Gronbaek H. Trefoil factors in inflammatory bowel disease. World J Gastroenterol. 2014;20(12):3223-30.
12. Philippeit C, Busch M, Dunker N. Epigenetic control of trefoil factor family (TFF) peptide expression in human retinoblastoma cell lines. Cell Physiol Biochem. 2014;34(3):1001-14.
13. Vestergaard EM, Nexo E, Torring N, Borre M, Orntoft TF, Sorensen KD. Promoter hypomethylation and upregulation of trefoil factors in prostate cancer. Int J Cancer. 2010;127(8):1857-65.
14. Longman RJ, Poulsom R, Corfield AP, Warren BF, Wright NA, Thomas MG. Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2006;54(12):1335-48.
15. Low D, Mizoguchi A, Mizoguchi E. DNA methylation in inflammatory bowel disease and beyond. World J Gastroenterol. 2013;19(32):5238-49.
16. Koike T, Shimada T, Fujii Y, Chen G, Tabei K, Namatame T, et al. Up-regulation of TFF1 (pS2) expression by TNF-alpha in gastric epithelial cells. J Gastroenterol Hepatol. 2007;22(6):936-42.
17. Muzes G, Molnar B, Tulassay Z, Sipos F. Changes of the cytokine profile in inflammatory bowel diseases. World J Gastroenterol. 2012;18(41):5848-61.
18. Dossinger V, Kayademir T, Blin N, Gott P. Down-regulation of TFF expression in gastrointestinal cell lines by cytokines and nuclear factors. Cell Physiol Biochem. 2002;12(4):197-206.
19. Gonzaga IM, Soares Lima SC, Nicolau MC, Nicolau-Neto P, da Costa NM, de Almeida Simao T, et al. TFF1 hypermethylation and decreased expression in esophageal squamous cell carcinoma and histologically normal tumor surrounding esophageal cells. Clin Epigenetics. 2017;9:130.
20. Rivas-Ortiz CI, Lopez-Vidal Y, Arredondo-Hernandez LJR, Castillo-Rojas G. Genetic Alterations in Gastric Cancer Associated with Helicobacter pylori Infection. Front Med (Lausanne). 2017;4:47.

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