Receptor for Advanced Glycation End Products (RAGE) Polymorphisms In Inflammatory Bowel Disease
Study Details
Study Description
Brief Summary
The inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that manifests as Crohn's disease (CD) and Ulcerative colitis (UC . Over the last two decades the incidence pattern of UC showed significant increase in previously low incidence areas such as Asia and the Middle East. In addition to microbial and environmental factors influencing IBDs, they are complex genetically, where hundreds of genetic loci contribute to disease susceptibility . Genome-wide association studies (GWAS) have identified several genetic susceptibility loci for UC and CD. Among the genetic factors involved, there are several single nucleotide polymorphisms (SNP) in molecules of the immune system associated with either susceptibility or protective effects to IBD progression, but with contradictory associations, mainly depending on the onset (adult or pediatric), sample size differences, inadequate statistical power and on the ethnicity-dependent genetic background. Growing evidence indicates that (RAGE) is involved in chronic inflammation and cancer. It is a transmembrane receptor normally expressed at low levels on a wide range of cells, bind a broad spectrum of ligands. Activated RAGE induces the synthesis of proinflammatory molecules resulting in magnifying rather than dampening inflammation . The human RAGE gene is located on chromosome 6p21.3, in the so-called class III of the major histocompatibility complex. The SNP at the -374A/T and -429T/C of the promoter region have been shown to increase protein synthesis threefold and twofold, respectively. Few studies found that RAGE is up-regulated in IBD, and it appears to play a role in the mechanisms involved in chronic inflammation Little information is available on the possible association of such polymorphisms with IBD. Few studies was carried out in different countries to assess these polymorphisms in IBD, resulting in conflicting results, between supporting and denial of the association. Due to this discrepancy we aimed to study this gene in our community including IBD patients.
| Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
This study aims:
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To investigate the association of both allelic and genotypic -374T/A and -429T/C polymorphisms and inflammatory bowel disease.
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To correlate the relation between the studied SNPs , disease activity and the clinical features of the disease.
Subjects and Methods:
This is a case control study. The study will include 90 patients diagnosed as IBD. Patients will be recruited from outpatient department of Elraghey Liver Hospital in Assiut University Hospital.The clinical disease activity was calculated using the Montreal classification of disease activity and Crohn's Disease Activity Index (CDAI) for UC and CD patients, respectively (Silverberg et al., 2005).
-Also, 90 apparently healthy subjects (age and sex matched with the patient group) will be included as control group.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Control Group 90 Apparently healthy individuals |
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| IBD group 90 Previously or Newly Diagnosed Ulcerative Colitis and Crohn's disease |
Outcome Measures
Primary Outcome Measures
- Association Of gene polymorphisms -374T/A and -429T/C in IBD patients [2020- 2023]
Compare the percentage of the polymorphism in Controls vs Patients
Secondary Outcome Measures
- To correlate the relation between the studied SNPs , disease activity and the clinical features of the disease [2020-2023]
find If there is a relation between the Found SNPs and disease activity and feature
Eligibility Criteria
Criteria
Inclusion Criteria: Egyprian IBD patients Attending ElRaghy Hospital in Assuit University hopital
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Exclusion Criteria:
- Exclusion criteria included the presence of neurological or cardiovascular diseases, diabetes, acute systemic illnesses, and previous or current history of cancer.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assiut University
Investigators
- Principal Investigator: Elham Abdelsamie, Assiut University
Study Documents (Full-Text)
None provided.More Information
Publications
- Ciccocioppo R, Bozzini S, Betti E, Imbesi V, Klersy C, Lakyova LS, Sukovsky L, Benacka J, Kruzliak P, Corazza GR, Di Sabatino A, Falcone C. Functional polymorphisms of the receptor for the advanced glycation end product promoter gene in inflammatory bowel disease: a case-control study. Clin Exp Med. 2019 Aug;19(3):367-375. doi: 10.1007/s10238-019-00562-x. Epub 2019 Jun 7.
- Girardelli M, Basaldella F, Paolera SD, Vuch J, Tommasini A, Martelossi S, Crovella S, Bianco AM. Genetic profile of patients with early onset inflammatory bowel disease. Gene. 2018 Mar 1;645:18-29. doi: 10.1016/j.gene.2017.12.029. Epub 2017 Dec 15.
- Hudson BI, Stickland MH, Futers TS, Grant PJ. Effects of novel polymorphisms in the RAGE gene on transcriptional regulation and their association with diabetic retinopathy. Diabetes. 2001 Jun;50(6):1505-11.
- Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Büning C, Cohain A, Cichon S, D'Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H; International IBD Genetics Consortium (IIBDGC), Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012 Nov 1;491(7422):119-24. doi: 10.1038/nature11582.
- Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, Panaccione R, Ghosh S, Wu JCY, Chan FKL, Sung JJY, Kaplan GG. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017 Dec 23;390(10114):2769-2778. doi: 10.1016/S0140-6736(17)32448-0. Epub 2017 Oct 16. Review. Erratum in: Lancet. 2020 Oct 3;396(10256):e56.
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- Schmidt AM, Yan SD, Yan SF, Stern DM. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest. 2001 Oct;108(7):949-55. Review.
- Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2010;28:367-88. doi: 10.1146/annurev.immunol.021908.132603. Review.
- Sugaya K, Fukagawa T, Matsumoto K, Mita K, Takahashi E, Ando A, Inoko H, Ikemura T. Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3. Genomics. 1994 Sep 15;23(2):408-19.
- Zallot C, Peyrin-Biroulet L. Deep remission in inflammatory bowel disease: looking beyond symptoms. Curr Gastroenterol Rep. 2013 Mar;15(3):315. doi: 10.1007/s11894-013-0315-7. Review.
- Polymorphisms in IBD