Türk popülasyonundaki ülseratif kolitli hastalarda TLR1(RS4833095) gen polimorfizminin hastalıkla ilişkisinin değerlendirilmesi
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Dosyalar
Tarih
2018
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Ülseratif kolit; kolonun mukozal tabakasında sınırlı, tekrarlayan inflamasyon dönemleri ile seyreden bir hastalıktır. Ülseratif kolit; genetik ve çevresel etmenlerin kombine etkisi sonucu ortaya çıkan multifaktöriyel bir hastalıktır. Birçok proinflamatuvar sitokinin ülseratif kolit etyolojisinde rol aldığı gösterilmiştir.(IL 23 R, TNF alpha, IL 27 … ) Toll like reseptörler, mikrobiyal antijenleri saptayan ve antijenlere karşı yanıt oluşturan ökaryotik hücre yüzey molekülleridir. TLR sinyal yolağındaki son ortak yol transkripsiyon faktörlerini içerir; NFB ve aktive edici protein 1 (AP -1) . Bu transkripsiyon faktörleri; önemli proinflamatuvar sitokinleri kodlayan (TNF, IL1, IL6, IL8, IL12 gibi) birçok geni düzenler. Bu çalışmada; Türk popülasyonunda Ülseratif kolitli hastalardaki TLR1(rs4833095) single nükleotid polimorfizminin değerlendirilmesi ve sağlıklı popülasyonla karşılaştırılması, tanımlanan polimorfizmlerin hastalıkla ilişkisinin değerlendirilmesi, tanımlanan single nükleotid polimorfizmlerinin hastalığın yayılımı ve şiddeti ile ilişkisinin değerlendirilmesi amaçlanmaktadır. Materyal metod: Çalışmaya Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi Gastroenteroloji kliniğinde ülseratif kolit tanısıyla takipli 18 yaş üstünde 90 hasta ve 18 yaş üzerinde 90 kişiden oluşan sağlıklı kontrol grubu dahil edildi. Çalışmaya alınan hastaların aldıkları medikal tedavi, laboratuvar verileri, koloskopi raporları ve bulguları, ekstraintestinal manifestasyonları ile ilgili veriler hastane kayıt sistemi retrospektif olarak taranarak elde edildi. Çalışmaya alınan hastalardan ve sağlıklı kontrollerden 3-4 cc kan örneği EDTA'lı tüplere alındı. Örnekler DNA izolasyonu yapılana kadar -80°C' de saklandı. DNA'lar izole edildikten sonra, elde edilen DNA' ların kalitesi nanogen spektrofotometri ile kontrol edildi. Kaliteli DNA' lar RT-PCR ile TLR1(RS 4833095) single nükleotid polimorfizmi açısından değerlendirildi. İstatiksel analizler için IBM SPSS versiyon 22.0 programı kullanıldı. Sayısal değişkenler ortalama ± standart sapma ile kategorik değişkenler ise sayı ve yüzde ile gösterildi. Gruplar arası kategorik verilerin karşılaştırılması için Chi-square testi kullanıldı. Anlamlılık düzeyi p<0,05 olarak kabul edildi. Bulgular: Türk popülasyonunda TLR1(RS4833095) single nükleoitid polimorfizminin ülseratif kolit için artmış riskle ilişkisi bulunmadı.(p>0,05) Türk popülasyonunda TLR1(RS4833095) single nükleotid polimorfizmi ile hastalığın kolondaki yayılımı arasında anlamlı ilişki saptanmadı.(p>0,05) Türk popülasyonunda TLR1(RS4833095) single nükleotid polimorfizmi ile hastalığın şiddeti ve remisyon sağlanması için gerekli tedavi arasında anlamlı ilişki saptanmadı.(p>0,05) Sonuç: Ülseratif kolit çevresel, genetik, konağa bağlı faktörlerin kombine etkisi sonucu meydana gelen bir hastalıktır. Etyopatogenezinde immündisregülasyonun rol oynadığına dair önemli kanıtlar vardır. Bakteriyel veya viral DNA, flagellin veya lipopolisakkarit(LPS) gibi Patojen İlişkili Moleküler Pattern'ler TLR'ler tarafından bağlanabilir ve birçok pro- ve antiinflamatuvar sitokini aktive ederek inflamasyonu indükleyebilir. Bank'ın Danimarkalı kohortta yaptığı çalışmada TLR1(RS4833095) homozigot varyant genotipinin ülseratif kolit gelişimi için artmış riskle ilişkisi bulunmasına rağmen Türk popülasyonunda yapılan çalışmada anlamlı fark bulunmamıştır. Sonuç olarak genetik polimorfizm çalışmaları coğrafik dağılımlara göre farklılık göstermektedir. Anahtar Kelimeler: ülseratif kolit, toll like reseptör, single nukleotid polimorfizm
Ulcerative colitis is a disease, limited to the mucosal layer of the colon and characterized by recurring inflammatory periods of the colon. Ulcerative colitis is a multifactorial disease that results from combined effects of genetic and environmental factors. Several proinflammatory cytokines have been shown to play a role in the etiology of ulcerative colitis. (IL 23 R, TNF alpha, IL 27 … ) Toll-like receptors are eukaryotic cell surface molecules that detect microbial antigens and respond to antigens. The last common pathway in the TLR signaling pathway involves transcription factors; NFB and activating protein 1 (AP -1). These transcription factors regulate genes which encodes important proinflammatory cytokines (such as TNF IL1 , IL 6, IL 8, IL 12...). In this trial, we aim to evaluate TLR1 (rs4833095) single nucleotide polymorphism in patients with ulcerative colitis and to compare with healthy population in the Turkish population. We also aim to evaluate the relation between the defined polymorphism and the risk of developing disease and the severity of the disease and the extension of the colon of the disease in the Turkish population. Materials and method: 90 patients, up to 18 years old, with ulcerative colitis that are outpatients in the gastroenterology clinic of the N.E.U. Meram Faculty of Medicine are included into the trial. 90 healthy controls, up to 18 years old, also are included. Data, which is about medical treatment, laboratory findings, colonoscopy reports and findings, extraintestinal manifestations of patients, is obtained by scanning hospital registry system retrospectively. 3-4 cc blood samples were taken into the tube, which has EDTA, from participants. All samples were kept at -80°C. After DNA isolation, the quality of obtained DNAs was checked by nanogen spectrophotometry. The DNAs of all patients and the control group were evaluated for polymorphism by using RT-PCR. SPSS 22.0 software program is used for the data entry and analysis, for the summary of the data concerning categorical variables the numbers and percentages are used. Mean ± standard deviation and median values were used for the numerical variables. Pearson Chi-square test was used to determine the relationships between the categorical data. The results were found to be statistically significant, with 95% confidence interval and the p-value less than 0.05. Findings: TLR1(rs4833095) single nucleotid polymorphisms weren't associated with increased risk of ulcerative colitis in the Turkish population(p>0,05). TLR1(rs4833095) single nucleotid polymorphisms weren't associated with extension of the colon of the disase in the Turkish population(p>0,05). TLR1(rs4833095) single nucleotid polymorphisms weren't associated with the severity of the disease in the Turkish population (p>0,05). Conclusion: Chronic inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are complex diseases that result from the interaction of numerous genetic and environmental factors TLR signaling pathways are involved in the autoimmune response to Pathogen-Associated Molecular Patterns (PAMPs) such as bacterial or viral DNA, flagellin or lipopolysaccharide (LPS). PAMPs can be bound by the membrane bound TLRs and induce inflammation by activating a number of pro- and anti-inflammatory cytokines The homozygous variant genotype of TLR1 743 T>C (rs4833095) (p = 0.004) was associated with increased risk of UC in the Danish cohort in the trial by Bank and friends. But in the Turkish population, there was no association between the homozygous variant genotype of TLR1 743 T>C (rs4833095) and the risk of ulcerative colitis (p>0,05). As a result, the trials of the genetic polymorphism are differed by geographical distribution. Keywords: ulcerative colitis, toll like receptor, single nukleotid polymorphism.
Ulcerative colitis is a disease, limited to the mucosal layer of the colon and characterized by recurring inflammatory periods of the colon. Ulcerative colitis is a multifactorial disease that results from combined effects of genetic and environmental factors. Several proinflammatory cytokines have been shown to play a role in the etiology of ulcerative colitis. (IL 23 R, TNF alpha, IL 27 … ) Toll-like receptors are eukaryotic cell surface molecules that detect microbial antigens and respond to antigens. The last common pathway in the TLR signaling pathway involves transcription factors; NFB and activating protein 1 (AP -1). These transcription factors regulate genes which encodes important proinflammatory cytokines (such as TNF IL1 , IL 6, IL 8, IL 12...). In this trial, we aim to evaluate TLR1 (rs4833095) single nucleotide polymorphism in patients with ulcerative colitis and to compare with healthy population in the Turkish population. We also aim to evaluate the relation between the defined polymorphism and the risk of developing disease and the severity of the disease and the extension of the colon of the disease in the Turkish population. Materials and method: 90 patients, up to 18 years old, with ulcerative colitis that are outpatients in the gastroenterology clinic of the N.E.U. Meram Faculty of Medicine are included into the trial. 90 healthy controls, up to 18 years old, also are included. Data, which is about medical treatment, laboratory findings, colonoscopy reports and findings, extraintestinal manifestations of patients, is obtained by scanning hospital registry system retrospectively. 3-4 cc blood samples were taken into the tube, which has EDTA, from participants. All samples were kept at -80°C. After DNA isolation, the quality of obtained DNAs was checked by nanogen spectrophotometry. The DNAs of all patients and the control group were evaluated for polymorphism by using RT-PCR. SPSS 22.0 software program is used for the data entry and analysis, for the summary of the data concerning categorical variables the numbers and percentages are used. Mean ± standard deviation and median values were used for the numerical variables. Pearson Chi-square test was used to determine the relationships between the categorical data. The results were found to be statistically significant, with 95% confidence interval and the p-value less than 0.05. Findings: TLR1(rs4833095) single nucleotid polymorphisms weren't associated with increased risk of ulcerative colitis in the Turkish population(p>0,05). TLR1(rs4833095) single nucleotid polymorphisms weren't associated with extension of the colon of the disase in the Turkish population(p>0,05). TLR1(rs4833095) single nucleotid polymorphisms weren't associated with the severity of the disease in the Turkish population (p>0,05). Conclusion: Chronic inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are complex diseases that result from the interaction of numerous genetic and environmental factors TLR signaling pathways are involved in the autoimmune response to Pathogen-Associated Molecular Patterns (PAMPs) such as bacterial or viral DNA, flagellin or lipopolysaccharide (LPS). PAMPs can be bound by the membrane bound TLRs and induce inflammation by activating a number of pro- and anti-inflammatory cytokines The homozygous variant genotype of TLR1 743 T>C (rs4833095) (p = 0.004) was associated with increased risk of UC in the Danish cohort in the trial by Bank and friends. But in the Turkish population, there was no association between the homozygous variant genotype of TLR1 743 T>C (rs4833095) and the risk of ulcerative colitis (p>0,05). As a result, the trials of the genetic polymorphism are differed by geographical distribution. Keywords: ulcerative colitis, toll like receptor, single nukleotid polymorphism.
Açıklama
Anahtar Kelimeler
Kolit-ülseratif, Colitis-ulcerative, Polimorfizm-genetik, Polymorphism-genetic, Reseptörler-toll like, Receptors-toll like
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Çağlayan, D. (2018). Türk popülasyonundaki ülseratif kolitli hastalarda TLR1(RS4833095) gen polimorfizminin hastalıkla ilişkisinin değerlendirilmesi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Dahili Tıp Bilimleri İç Hastalıklar Anabilim Dalı, Konya.
