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

NCT ID: NCT04286659

Last Updated: 2020-02-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

180 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-03-01

Study Completion Date

2023-12-31

Brief Summary

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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.

Detailed Description

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This study aims:

1. To investigate the association of both allelic and genotypic -374T/A and -429T/C polymorphisms and inflammatory bowel disease.
2. 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.

Conditions

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Inflammatory Bowel Diseases

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

OTHER

Study Groups

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Control Group

90 Apparently healthy individuals

No interventions assigned to this group

IBD group

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

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

\-
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Noha Refaat Abdelhamid

Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Elham Abdelsamie

Role: PRINCIPAL_INVESTIGATOR

Assiut University

Central Contacts

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Noha R Abdelhamid

Role: CONTACT

01007304366

Abeer A Mokhtar

Role: CONTACT

01008792989

References

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Reference Type BACKGROUND
PMID: 23354742 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25584169 (View on PubMed)

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.

Reference Type BACKGROUND
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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.

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PMID: 29248579 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20192808 (View on PubMed)

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Reference Type BACKGROUND
PMID: 23128233 (View on PubMed)

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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
PMID: 7835890 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11375354 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31175506 (View on PubMed)

Other Identifiers

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Polymorphisms in IBD

Identifier Type: -

Identifier Source: org_study_id

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