Quantitative Evaluation of NOD2 Promoter Methylation Profiling in Colon Biopsy Samples from Ulcerative Colitis Patients and Non-Colitis Controls
-
Golshid Sanati
,
Mehrdad Noruzinia
,
Davood Jafari
,
Mohammad Ahmadvand
,
Shahram Teimourian
,
Naser Ebrahimi Daryani
,
Sara Hanaei
,
Nima Rezaei
Abstract
Background: Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with evidence addressing the role of epigenetic changes. The intention of this study was to detect the association of DNA methylation levels of NOD2 gene with UC and to evaluate whether any of these changes might be a useful biomarker for detecting patients with UC.
Methods: The methylation status of the promoter CpG islands (CGIs) of NOD2 gene was examined in the colonic mucosae of 15 cancer-free patients with UC and 15 age- and sex-matched healthy controls by the real-time quantitative multiplex-methylation specific PCR (QM-MSP) assay. Methylation-specific melting curve analysis (MS-MCA) was used to analyze the data.
Results: The median unmethylated DNA index was significantly higher in cases compared to controls, and hypormethylation of NOD2 gene was significantly correlated with UC (Unmethylated DNA in UC vs. HC; 0.102±0.055 vs. 0.025±0.016, P = 0.000).
Conclusion: The NOD2 gene that was differentially methylated in UC patients, provides new insights into the pathogenesis of UC, with a view to making steps toward the development of accurate biomarkers for diagnostic tools in UC.
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17. Kim H-J. Role of Nucleotide-binding and Oligomerization Domain 2 Protein (NOD2) in the Development of Atherosclerosis. Korean J Physiol & Pharmacol. 2015;19(6):479-84.
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24. Husseiny MI, Kuroda A, Kaye AN, Nair I, Kandeel FFerreri K. Development of a quantitative methylation-specific polymerase chain reaction method for monitoring beta cell death in type 1 diabetes. PloS one. 2012;7(10):e47942.
25. Liu J, Morgan M, Hutchison KCalhoun VD. A study of the influence of sex on genome-wide methylation. PloS one. 2010;5(4):e10028.
26. Ahuja N, Li Q, Mohan AL, Baylin SBIssa J-PJ. Aging and DNA methylation in colorectal mucosa and cancer. Cancer res. 1998;58(23):5489-94.
27. Issa J-PJ, Ottaviano YL, Celano P, Hamilton SR, Davidson NEBaylin SB. Methylation of the oestrogen receptor CpG island links aging and neoplasia in the human colon. Nat Genet. 1994;7(4):536-40.
28. Tahara T, Hirata I, Nakano N, Nagasaka M, Nakagawa Y, Shibata T, et al. Comprehensive DNA Methylation Profiling of Inflammatory Mucosa in Ulcerative Colitis. Inflamm Bowel Dis. 2017;23(1):165-73.
29. Glória L, Cravo M, Pinto A, de Sousa LS, Chaves P, Leitão CN, et al. DNA hypomethylation and proliferative activity are increased in the rectal mucosa of patients with long‐standing ulcerative colitis. Cancer. 1996;78(11):2300-6.
30. Leung E, Hong J, Fraser AG, Merriman TR, Vishnu P, Abbott WGH, et al. Polymorphisms of CARD15//NOD2 and CD14 genes in New Zealand Crohn/'s disease patients. Immunol Cell Biol. 2005;83(5):498-503.
2. Christophi GP, Rong R, Holtzapple PG, Massa PTLandas SK. Immune markers and differential signaling networks in ulcerative colitis and Crohn's disease. Inflamm bowel dis. 2012;18(12):2342-56.
3. Maul JZeitz M. Ulcerative colitis: immune function, tissue fibrosis, and current therapeutic considerations. Langenbeck's Arch Surg. 2012;397(1):1-10.
4. Conrad K, Roggenbuck DLaass MW. Diagnosis and classification of ulcerative colitis. Autoimmunity rev. 2014;13(4):463-6.
5. Parray FQ, Wani ML, Bijli AH, Thakur NIrshad I. Crohn’s disease: a surgeon’s perspective. Saudi Journal of Gastroenterology: official journal of the Saudi Gastroenterology Association. 2011;17(1):6.
6. Plevy S, Silverberg MS, Lockton S, Stockfisch T, Croner L, Stachelski J, et al. Combined serological, genetic, and inflammatory markers differentiate non-IBD, Crohn’s disease, and ulcerative colitis patients. Inflamm bowel dis. 2013;19(6):1139.
7. Gould NJ, Davidson KL, Nwokolo CUArasaradnam RP. A systematic review of the role of DNA methylation on inflammatory genes in ulcerative colitis. 2016.
8. Büning C, Molnar T, Nagy F, Lonovics J, Weltrich R, Bochow B, et al. NOD2/CARD15 gene polymorphism in patients with inflammatory bowel disease: is Hungary different? World Journal of Gastroenterology: WJG. 2005;11(3):407.
9. Doecke JD, Simms LA, Zhao ZZ, Huang N, Hanigan K, Krishnaprasad K, et al. Genetic susceptibility in IBD: overlap between ulcerative colitis and Crohn's disease. Inflamm bowel dis. 2013;19(2):240-5.
10. Ventham NT, Kennedy NA, Nimmo ERSatsangi J. Beyond gene discovery in inflammatory bowel disease: the emerging role of epigenetics. Gastroenterology. 2013;145(2):293-308.
11. Su LJ, Mahabir S, Ellison GL, McGuinn LAReid BC. Epigenetic contributions to the relationship between cancer and dietary intake of nutrients, bioactive food components, and environmental toxicants. Front Genet. 2011;2.
12. Low D, Mizoguchi AMizoguchi E. DNA methylation in inflammatory bowel disease and beyond. World Journal of Gastroenterology: WJG. 2013;19(32):5238.
13. Holliday R. DNA methylation and epigenotypes. Biochemistry (Moscow). 2005;70(5):500-4.
14. Moore LD, Le TFan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38(1):23.
15. Karatzas PS, Gazouli M, Safioleas MMantzaris GJ. DNA methylation changes in inflammatory bowel disease. Annals of Gastroenterology: a quarterly publication of the Hellenic Society of Gastroenterology. 2014;27(2):125.
16. Zhang Y-ZLi Y-Y. Inflammatory bowel disease: pathogenesis. World Journal of Gastroenterology: WJG. 2014;20(1):91.
17. Kim H-J. Role of Nucleotide-binding and Oligomerization Domain 2 Protein (NOD2) in the Development of Atherosclerosis. Korean J Physiol & Pharmacol. 2015;19(6):479-84.
18. Pugazhendhi S, Santhanam S, Venkataraman J, Creveaux IRamakrishna BS. NOD2 gene mutations associate weakly with ulcerative colitis but not with Crohn's disease in Indian patients with inflammatory bowel disease. Gene. 2013;512(2):309-13.
19. Berrebi D, Maudinas R, Hugot J, Chamaillard M, Chareyre F, De Lagausie P, et al. Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn’s disease colon. Gut. 2003;52(6):840-6.
20. Podolsky DK. Inflammatory Bowel Disease. New Eng J Med. 1991;325(14):1008-16.
21. Lo P-K, Watanabe H, Cheng P-C, Teo WW, Liang X, Argani P, et al. MethySYBR, a novel quantitative PCR assay for the dual analysis of DNA methylation and CpG methylation density. J Mol Diagn. 2009;11(5):400-14.
22. Li Y, Deuring J, Peppelenbosch MP, Kuipers EJ, de Haar Cvan der Woude CJ. IL-6-induced DNMT1 activity mediates SOCS3 promoter hypermethylation in ulcerative colitis-related colorectal cancer. Carcinogenesis. 2012:bgs214.
23. Schmittgen TDLivak KJ. Analyzing real-time PCR data by the comparative CT method. Nat protoc. 2008;3(6):1101-8.
24. Husseiny MI, Kuroda A, Kaye AN, Nair I, Kandeel FFerreri K. Development of a quantitative methylation-specific polymerase chain reaction method for monitoring beta cell death in type 1 diabetes. PloS one. 2012;7(10):e47942.
25. Liu J, Morgan M, Hutchison KCalhoun VD. A study of the influence of sex on genome-wide methylation. PloS one. 2010;5(4):e10028.
26. Ahuja N, Li Q, Mohan AL, Baylin SBIssa J-PJ. Aging and DNA methylation in colorectal mucosa and cancer. Cancer res. 1998;58(23):5489-94.
27. Issa J-PJ, Ottaviano YL, Celano P, Hamilton SR, Davidson NEBaylin SB. Methylation of the oestrogen receptor CpG island links aging and neoplasia in the human colon. Nat Genet. 1994;7(4):536-40.
28. Tahara T, Hirata I, Nakano N, Nagasaka M, Nakagawa Y, Shibata T, et al. Comprehensive DNA Methylation Profiling of Inflammatory Mucosa in Ulcerative Colitis. Inflamm Bowel Dis. 2017;23(1):165-73.
29. Glória L, Cravo M, Pinto A, de Sousa LS, Chaves P, Leitão CN, et al. DNA hypomethylation and proliferative activity are increased in the rectal mucosa of patients with long‐standing ulcerative colitis. Cancer. 1996;78(11):2300-6.
30. Leung E, Hong J, Fraser AG, Merriman TR, Vishnu P, Abbott WGH, et al. Polymorphisms of CARD15//NOD2 and CD14 genes in New Zealand Crohn/'s disease patients. Immunol Cell Biol. 2005;83(5):498-503.
| Files | ||
| Issue | Vol 4, No 4 (2021) | |
| Section | Original Article | |
| DOI | https://doi.org/10.18502/igj.v4i4.12757 | |
| Keywords | ||
| DNA Methylation Ulcerative Colitis Epigenetics NOD2 Biomarker | ||
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How to Cite
1.
Sanati G, Noruzinia M, Jafari D, Ahmadvand M, Teimourian S, Ebrahimi Daryani N, Hanaei S, Rezaei N. Quantitative Evaluation of NOD2 Promoter Methylation Profiling in Colon Biopsy Samples from Ulcerative Colitis Patients and Non-Colitis Controls. Immunol Genet J. 2021;4(4):196-202.
