Receptor for Advanced Glycation End Products (RAGE) Polymorphisms In Inflammatory Bowel Disease

NCT04286659 | Unknown

• 1 other identifier: Polymorphisms in IBD
• Study Type: observational
• Target: 180
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Inflammatory Bowel Diseases

Outcome Measures

Primary Outcomes (1)

• Association Of gene polymorphisms -374T/A and -429T/C in IBD patients

  Compare the percentage of the polymorphism in Controls vs Patients

  2020- 2023

Secondary Outcomes (1)

• To correlate the relation between the studied SNPs , disease activity and the clinical features of the disease

  2020-2023

Study Arms (2)

Control Group

90 Apparently healthy individuals

IBD group

90 Previously or Newly Diagnosed Ulcerative Colitis and Crohn's disease

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

90 Patients and 90 Healthy Controls

Sponsors & Collaborators

• Assiut University: lead

Related Publications (10)

• 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.

  PMID: 23354742 BACKGROUND

• Norouzinia M, Naderi N. Personalized management of IBD; is there any practical approach? Gastroenterol Hepatol Bed Bench. 2015 Winter;8(1):1-3. No abstract available.

  PMID: 25584169 BACKGROUND

• 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.

  PMID: 29050646 BACKGROUND

• 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.

  PMID: 29248579 BACKGROUND

• 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.

  PMID: 20192808 BACKGROUND

• 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, Buning 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.

  PMID: 23128233 BACKGROUND

• 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. doi: 10.1172/JCI14002. No abstract available.

  PMID: 11581294 BACKGROUND

• 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. doi: 10.1006/geno.1994.1517.

  PMID: 7835890 BACKGROUND

• 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. doi: 10.2337/diabetes.50.6.1505.

  PMID: 11375354 BACKGROUND

• 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.

  PMID: 31175506 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood Sample

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Elham Abdelsamie

  Assiut University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Noha R Abdelhamid

CONTACT

01007304366; noharefaat02@gmail.com

Abeer A Mokhtar

CONTACT

01008792989; Abeermokhtar2010@yahoo.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: February 27, 2020
• Study Start: March 1, 2020
• Primary Completion: March 1, 2023
• Study Completion: December 1, 2023
• Last Updated: February 27, 2020

Record last verified: 2020-02