The role of COX-2 gene variants on the disease mechanism of inflammatory bowel disease in a Turkish population

Aim: Inflammatory bowel disease has two major types: Crohn’s disease and ulcerative colitis that occur in the gastrointestinal tract with unknown etiology. COX-2 has important role on carcinogenesis process including colon cancer supporting the tumor growth. COX-2 was also known due to its ability to change homeostasis on colonic mucosa in inflammatory cells on patients who have inflammatory bowel disease. In this study, we have aimed to find a linkage between inflammatory bowel disease and COX-2 in a Turkish population. Methods:A total of 106 patients,42 with Crohn’s disease and 64 with ulcerative colitis and 121 healthy control subjects were included the study. Gene variants of COX-2-765G→C and COX-2-1195A→G were analyzed by polymerase chain reaction and restriction fragment length polymorphism techniques. Results: The results demonstrated that COX-2-1195A→G gene variants AA carriers were statistically found in high level on patients with both ulcerative colitis (p=0.001) and Crohn’s disease (p=0.008). In contrast, AG genotype and G carriers were statistically found higher in control group (Crohn’s disease, p=0.005 for AG and p= 0.008 for G; ulcerative colitis, p=0.001 for AG and p=0.001 for G). Conclusion: In this research, we have observed important and questionable results between inflammatory bowel disease and COX-2, especially COX-2-1195A→G gene variants AA carriers in a Turkish population. Researches need to focus on their local roles on inflammatory bowel disease pathogenesis with large sample size.

Türk toplumundaki inflamatuar bağırsak hastalığının hastalık mekanizmasında COX-2 gen varyantlarının rolü

Amaç: İnflamatuar bağırsak hastalığı, gastrointestinal sistemde etiolojisi tam olarak bilinmeyen bir hastalık grubu olup, Crohn hastalığı ve ülseratif kolit olmak üzere iki önemli tipe ayrılmaktadır. COX-2 kolon kanserinin de dahil olduğu karsinogenez prosesinde rolü olan ve tümör gelişimine katkı sağlayan bir mediatördür. Aynı zamanda, inflamasyon meydana geldiğinde kolonik mukoza üzerindeki stabiliteyi değiştirdiği bilinmektedir. Bu amaçla, çalışmamızda inflamatuar barsak hastalığı ile COX-2 ilişkisinin Türk kökenli kişiler üzerinde araştırılması amaçlanmıştır. Yöntemler: Çalışmaya 42 Crohn ve 64 ülseratif kolitli hasta olmak üzere toplam 106 hasta) ve 121 sağlıklı kontrol dahil edilmiştir. COX-2 -765G→C ve COX-2 -1195A→G gen varyantları polimeraz zincir reaksiyonu ve restriksiyon parça uzunluk polimorfizmi teknikleri kullanılarak analiz edilmiştir. Bulgular: COX-2-1195A→G gen varyantı AA taşıyıcılarının istatistiksel olarak hasta grubunda (Crohn hastalığı için p=0,008 ve ülseratif kolit için p=0,001) kontrol grubuna göre yüksek bulunmuştur. Buna karşılık olarak AG genotipi ve G taşıyıcıları da kontrol grubunda anlamlı olarak yüksek bulunmuştur (Crohn hastalığı: p=0,005 AG için ve p= 0,008 G için; ülseratif kolit: p=0,001 AG için ve p=0,001G için). Sonuç: Çalışmada Türk kökenli kişiler üzerinde, inflamatuar bağırsak hastalığı ve COX-2 arasındaki ilişkiye dair COX-2-1195A→G AA taşıyıcıları gibi önemli ve araştırılması gerekli soruları beraberinde getiren bulgular elde edilmiştir. Hasta sayısının arttırılarak ek çalışmalar ile hastalık patogonezindeki rolünün tam olarak araştırılması gerektiği düşünülmektedir.

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Sleizenger & Fordtran’s, Gastrointestinal and Liver Disease 7th Edition, Saunders Elsevier, Philadelphia .Volume I, pp. 2005–67.

Peña-Sánchez JN, Lix LM, Teare GF, Li W, Fowler SA, Jones JL. Impact of an Integrated Model of Care on Outcomes of Patients With Inflammatory Bowel Diseases: Evidence From a Population-Based Study. J Crohns Colitis. 2017;11:1471-9.

Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–35.

Higashi D, Futami K, Ishibashi Y, Egawa Y, Maekawa T, Matsui T, Iwashita A, et al. Clinical course of colorectal cancer in patients with ulcerative colitis. Anticancer Res. 2011;31:2499–504.

Lesage S, Zouali H, Cézard JP, Colombel JF, Belaiche J, Almer S, et al. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet. 2002;70:845-57.

Olén O, Askling J, Sachs MC, Frumento P, Neovius M, Smedby KE, et al. Childhood onset inflammatory bowel disease and risk of cancer: a Swedish nationwide cohort study 1964-2014. BMJ. 2017;20:358:j3951.

Jewel Samadder N, Valentine JF, Guthery S, Singh H, Bernstein CN, Wan Y, et al. Colorectal Cancer in Inflammatory Bowel Diseases: A Population-Based Study in Utah. Dig Dis Sci. 2017;62:2126-32.

Luo C, Zhang H. The Role of Proinflammatory Pathways in the Pathogenesis of Colitis-Associated Colorectal Cancer. Mediators Inflamm. 2017;2017:5126048.

Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126:451–9.

Wang R, Leong RW. Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: a review of the literature. World J Gastroenter. 2014;20:8783– 9

Watanabe T, Konishi T, Kishimoto J, Kotake K, Muto T, Sugihara K, et al. Ulcerative colitis-associated colorectal cancer shows a poorer survival than sporadic colorectal cancer: a nationwide Japanese study. Inflamm Bowel Dis. 2011;17:802–8.

Zhang X, Miao X, Tan W, Ning B, Liu Z, Hong Y. Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. Gastroenterology. 2005;129:565–76.

Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population based study. Cancer. 2001;91:854-62.

Goldacre MJ, Wotton CJ, Yeates D, Seagroatt V, Jewell D. Cancer in patients with ulcerative colitis, Crohn’s disease and coeliac disease: record linkage study. Eur J Gastroenterol Hepatol. 2008;20:297-304.

Beaugerie L, Svrcek M, Seksik P, Bouvier AM, Simon T, Allez M, et al. CESAME Study Group. Risk of colorectal high-grade dysplasia and cancer in a prospective observational cohort of patients with inflammatory bowel disease. Gastroenterology. 2013;145:166-175.e8.

Askling J, Dickman PW, Karlén P, Broström O, Lapidus A, Löfberg R,et al. Family history as a risk factor for colorectal cancer in inflammatory bowel disease. Gastroenterology. 2001;120:1356-62.

Thompson PA, Ashbeck EL, Roe DJ, Fales L, Buckmeier J, Wang F, et al. Celecoxib for the Prevention of Colorectal Adenomas: Results of a Suspended Randomized Controlled Trial. J Natl Cancer Inst. 2016;108:pii:djw151.

Li P, Wu H, Zhang H, Shi Y, Xu J, Ye Y, et al. Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis. Gut. 2015;64:1419-25.

Connell W, Leong RW, Walsh A, Kamm M, Kench J, What should be the protocol to manage indefinite dysplasia in IBD? http://wiki.cancer.org.au/australiawiki/index.php?oldid=17938, 2012.

Singer II, Kawka DW, Schloemann S, Tessner T, Riehl T, Stenson WF, Cyclooxygenase 2 is induced in colonicepithelial cells in inflammatory bowel disease. Gastroenterology. 1998;115:297–306.

Smythe EM, Burke A, FitzGerald GA. Lipid-derived autacoids: eicosanoids and platelet-activating factor. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, edited by Brunton LL, Lazo JS, Parker KL. New York: McGraw-Hill, 2005, pp. 653–70.

Patrignani P, Panara MR, Sciulli MG, Santini G, Renda G, Patrono C. Differential inhibition of human prostaglandin endoperoxide synthase1 and -2 by nonsteroidal anti-inflammatory drugs. J Physiol Pharmacol. 1997;48:623–31.

Vane JR, Botting RM. New insights into the mode of action of antiinflammatory drugs. Inflamm Res. 1995;44:1–10.

Needleman P, Isakson PC. The discovery and function of COX-2. J Rheumatol. 1997;49:6–8.

Jones MK, Wang H, Peskar BM, Levin E, Itani RM, Sarfeh IJ, et al. Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growthand ulcer healing. Nat Med. 1999;5:1418–23.

Hatazawa R, Tanaka A, Tanigami M, Amagase K, Kato S, Ashida Y, Takeuchi K. Cyclooxygenase-2/prostaglandin E2 accelerates the healing of gastric ulcers via EP4 receptors. Am J Physiol Gastrointest Liver Physiol. 2007;293:G788–G797.

Mizuno H, Sakamoto C, Matsuda K, Wada K, Uchida T, Noguchi H, et al. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology. 1997;112:387–97.

Ukawa H, Yamakuni H, Kato S, Takeuchi K. Effects of cyclooxygenase- 2 selective and nitric oxide-releasing nonsteroidal antiinflammatory drugs on mucosal ulcerogenic and healing responses of the stomach. DigDis Sci. 1998;43:2003–11.

Andersen V, Nimmo E, Krarup HB, Drummond H, Christensen J, Ho GT, et al. Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in a Scottish and Danish case-control study. Inflamm Bowel Dis. 2011;17:937-46.

Zhang CX, Guo LK, Guo XF. Interaction between the polymorphisms of cyclooxygenase-2-1195G/A,MnSOD9Ala/val genes and the high-fat diets and its correlation with ulcerative colitis. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2015;37: 37-43.

de Vries HS, te Morsche RH, van Oijen MG, Nagtegaal ID, Peters WH, de Jong DJ.The functional -765G→C polymorphism of the COX2 gene may reduce the risk of developing crohn's disease. PLoS One. 2010;5:e15011.

Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 1999;8:7908-16.

Zhu W, Wei BB, Shan X, Liu P. -765G>C and 8473T> C polymorphisms of COX-2 and cancer risk: a meta-analysis based on 33 case–control studies. Mol Biol Rep. 2009;37:277–88.

Watanabe J, Lin JA, Narasimha AJ, Shahbazian A, Ishikawa T, Martin MG, et al. Novel anti-inflammatory functions for endothelial and myeloid cyclooxygenase-2 in a new mouse model of Crohn’s disease. Am J Physiol Gastrointest Liver Physiol. 2010;298:G842– G850.
Archives of Clinical and Experimental Medicine-Cover
  • ISSN: 2564-6567
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2016
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