Türk popülasyonundaki ülseratif kolitli hastalarda TLR1(RS4833095) gen polimorfizminin hastalıkla ilişkisinin değerlendirilmesi

Yıl 2024, Cilt: 34 Sayı: 5, 603 - 608, 30.10.2024

Dilek Çağlayan , Ramazan Dertli , Melek Çağlayan , Mahmut Selman Yıldırım , Hüseyin Ataseven

https://doi.org/10.54005/geneltip.1387463

Öz

Amaç: Ülseratif Kolit, kolonun mukozal tabakasında tekrarlayan inflamasyon dönemleri ile karakterize olan çok faktörlü bir hastalıktır. Toll benzeri reseptörler (TLR'ler), pro/anti-inflamatuar genlerin uyarılmasında ve adaptif immün yanıtların kontrolünde anahtar rol oynayan transmembran, patern tanıma reseptörleridir. Bu çalışmada TLR1(rs4833095) tek nükleotid polimorfizmi ile ülseratif kolit arasındaki ilişkiyi değerlendirmeyi amaçladık.
Yöntem: Çalışmaya 90 ülseratif kolit hastası ve 90 kişiden oluşan sağlıklı kontrol grubu dahil edildi. Çalışmaya dahil edilen hastaların aldıkları tıbbi tedaviler, laboratuvar verileri, kolonoskopi bulguları, bağırsak dışı bulguları kaydedildi. TLR1(rs4833095) tek nükleotid polimorfizmi RT-PCR yöntemiyle çalışıldı.
Bulgular: Türk toplumunda TLR1(rs4833095) tek nükleotid polimorfizmi olan ülseratif kolit hastalarında ülseratif kolit riskinde artış saptanmadı (p>0,05). Çalışmamızda TLR 1(rs4833095) tek nükleotid polimorfizmi ile hastalığın kolondaki yayılımı, hastalığın şiddeti ve remisyon için gerekli tedavi arasında ilişki saptanmadı(p>0,05).
Sonuç: Türk toplumunda TLR1 (rs4833095) tek nükleotid polimorfizmi değerlendirilmiş ve ülseratif kolitli hastalar ile kontrol grubu arasında anlamlı fark saptanmamıştır.

Anahtar Kelimeler

: Ülseratif kolit, toll benzeri reseptörler, inflamatuar barsak hastalığı, tek nükleotid polimorfizmi.

Evaluation of the relationship between TLR1(RS4833095) gene polymorphism and disease in patients with ulcerative colitis in the Turkish population

Öz

Background: Ulcerative Colitis is a multifactorial disease which is characterized by recurrent periods of inflammation in the mucosal layer of the colon. Toll-like receptors (TLRs) are a class of transmembrane pattern recognition receptors that play a key role in the induction of pro/anti-inflammatory genes and in the control of adaptive immune responses. In this study, we aimed to evaluate the relation between TLR1(rs4833095) single nucleotide polymorphism and ulcerative colitis.
Methods: The study included 90 patients with ulcerative colitis and a healthy control group consisting of 90 people. Taken medical treatment, laboratory data, colonoscopy findings, extraintestinal manifestations of patients included in this study were recorded. TLR1(rs4833095) single nucleotide polymorphism was studied with RT-PCR methods.
Results: There was no increased risk for ulcerative colitis in patients with ulcerative colitis who has TLR1(rs4833095) single nucleotide polymorphism in Turkish population (p>0.05). There was no association between TLR 1(rs4833095) single nucleotide polymorphism and the spread of the disease in the colon, severity of disease and treatment required for remission in our study(p>0.05).
Conclusion: In the Turkish population, TLR1 (rs4833095) single nucleotide polymorphism was evaluated and no significant difference was found between the patients with ulcerative colitis and the control group.

Anahtar Kelimeler

Ulcerative colitis, toll-like receptors, inflammatory bowel disease, single nucleotide polymorphism.

Destekleyen Kurum

N.E.Ü BAP (Bilimsel Araştırma Projeleri)

Kaynakça

• Friedman S, Blumberg RS, editors. Inflammatory Bowel Disease. Harrison’s Principles of Internal Medicine; 2013.p.1886-7
• Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347: 417–29.
• Medzhitov R, Preston-Hurlburt P, Janeway CA. A humanhomologue of theDrosophilaToll protein signalsactivation of adaptiveimmunity. Nature 1997; 388(6640): 394-7.
• Poltorak A, Smirnova I, He X, Liu MY, Huffel CF, Birdwell D, et al. Genetic and physical mapping of the Lps locus: identification of the toll-4 receptor as a candidate gene in the critical region. Blood Cells Mol Dis 1998; 24:340–55.
• Cario E. Toll-like receptors in inflammatory bowel diseases: a decade later. Inflamm Bowel Dis 2010; 16: 1583–97.
• Bank S, Skytt AP, Burisch J, Pedersen N, Roug S, Galsgaard J, et al. Polymorphisms in the Inflammatory Pathway Genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG Are Associated with Susceptibility of Inflammatory Bowel Disease in a Danish Cohort. PLoS One 2014; 9: e98815.
• Anderson CA, Boucher G, Lees CW, Franke A, D' Amato M, Taylor KD, et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 2017; 43: 246–52.
• Thompson AI, Lees CW. Genetics of ulcerative colitis. Inflamm Bowel Dis 2011; 17: 831-48.
• Verstrepen L, Bekaert T, Chau TL, Tavernier J, Chariot A, Beyaert R. TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme. Cell Mol Life Sci 2008; 65: 2964–78.
• Cario E, Podolsky DK. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000;68: 7010–17.
• Cario E, Rosenberg IM, Brandwein SL, Beck PL, Reinecker HC, Podolsky DK, et al. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J Immunol. 2000; 164:966–72.
• Abreu MT, Vora P, Faure E, Thomas LS, Arnold ET, Arditi M, et al. Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J Immunol2001;167: 1609–16.
• Ortega-Cava CF, Ishihara S, Rumi MA, Kawashima K, Ishimura N, Kazumori H, et al. Strategic compartmentalization of Toll-like receptor 4 in the mouse gut. J Immunol. 2003; 170:3977–85.
• Otte JM, Cario E, Podolsky DK. Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells. Gastroenterology. 2004; 126:1054–70.
• Singh JC, Cruickshank SM, Newton DJ, Wakenshaw L, Graham A, Lan J, et al. Toll-like receptor-mediated responses of primary intestinal epithelial cells during the development of colitis. Am J PhysiolGastrointest Liver Physiol2005;288: 514–24.
• Rumio C, Besusso D, Palazzo M, Selleri S, Sfondrini L, Dubini F. et al, Degranulation of Paneth cells via toll-like receptor 9. Am J Pathol2004;165: 373–81.
• Vaishnava S, Behrendt CL, Ismail AS, Eckmann L, Hooper L. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc Natl AcadSci U S A. 2008; 105:20858–63.
• Podolsky DK, Gerken G, Eyking A, Cario E. Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency. Gastroenterology 2009;137: 209–20.
• Bogunovic M, Dave SH, Tilstra JS, Chang DTW, Harpaz N, Xiong H, et al. Enteroendocrine cells express functional Toll-like receptors. Am J PhysiolGastrointest Liver Physiol2007; 292: 1770–83.
• Palazzo M, Balsari A, Rossini A, Selleri S, Calcaterra C, Gariboldi S, et al. Activation of enteroendocrine cells via TLRs induces hormone, chemokine, and defensin secretion. J Immunol 2007;178: 4296–303.
• Otte JM, Rosenberg IM, Podolsky DK. Intestinal myofibroblasts in innate immune responses of the intestine. Gastroenterology 2003;124: 1866–78.
• Walton KL, Holt L, Sartor RB. Lipopolysaccharide activates innate immune responses in murine intestinal myofibroblasts through multiple signaling pathways. Am J PhysiolGastrointest Liver Physiol 2009;296: 601–11.
• Smith PD, Smythies LE, Mosteller-Barnum M, Sibley DA, Russell MW, Merger M, et al. Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. J Immunol2001;167: 2651–66.
• Hausmann M, Kiessling S, Mestermann S, Webb G, Spottl T, Andus T, et al. Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology 2002;122: 1987–2000.
• Hart AL, Al-Hassi HO, Rigby RJ, Bell SJ, Emmanuel AV, Knight SC, et al. Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 2005;129: 50–65.
• Uematsu S, Jang MH, Chevrier N, Guo Z, Kumagai Y, Yamamoto M, et al. Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells. Nat Immunol2006;7: 868–74.
• Tomita T, Kanai T, Fujii T, Nemoto Y, Okamoto R, Tsuchiya K, et al. MyD88-Dependent Pathway in T Cells Directly Modulates the Expansion of Colitogenic CD4+ T Cells in Chronic Colitis. J Immunol 2008;180: 5291–99.
• Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007;448: 427–34.
• Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009;361: 2066–78.
• Ge X, Wen H, Fei Y, Xue R, Cheng Z, Li Y, Cai K, Li L, Li M, Luo Z. Structurally dynamic self-healable hydrogel cooperatively inhibits intestinal inflammation and promotes mucosal repair for enhanced ulcerative colitis treatment. Biomaterials. 2023;299:122184.
• Elkholy SE, Maher SA, Abd El-Hamid NR, Elsayed HA, Hassan WA, Abdelmaogood AKK, Hussein SM, Jaremko M, Alshawwa SZ, Alharbi HM, Imbaby S. The immunomodulatory effects of probiotics and azithromycin in dextran sodium sulfate-induced ulcerative colitis in rats via TLR4-NF-κB and p38-MAPK pathway. Biomed Pharmacother. 2023;165:115005.
• Wen X, Xie R, Wang HG, Zhang MN, He L, Zhang MH, Yang XZ. Fecal microbiota transplantation alleviates experimental colitis through the Toll-like receptor 4 signaling pathway. World J Gastroenterol. 2023 Aug 14;29(30):4657-4670. doi: 10.3748/wjg.v29.i30.4657. PMID: 37662857; PMCID: PMC10472902.
• Bank S, Skytt AP, Burisch J, Pedersen N, Roug S, Galsgaard J, et al. Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort.PLoS One 2015; 10(12): e0145302.