RORC Genetic Polymorphism of Rheumatoid Arthritis

NCT ID: NCT03615729

Last Updated: 2018-08-06

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

COMPLETED

Total Enrollment

89 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-06-30

Study Completion Date

2018-06-30

Brief Summary

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Three candidate single nucleotide polymorphisms in the RORC2 gene, rs9826 A/G, rs3790515 C/T and rs3828057 C/T were examined together with estimation of nuclear hormone retinoic acid receptor-related orphan receptor variant 2 serum levels to determine their possible association with susceptibility to and clinical phenotype of rheumatoid arthritis in Egyptian population.

Detailed Description

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Rheumatoid arthritis is a chronic systemic inflammatory arthritis that affects about one percent of the population. It results from a complex interaction between genes and environment (eg, external trigger as cigarette smoking, infection, or trauma) leading to a breakdown of immune tolerance, synovial inflammation and hypertrophy and chronic joint inflammation in a characteristic symmetric pattern.

The role of T helper 17 cells and T helper 17 cells -associated cytokines in the pathogenesis of rheumatoid arthritis is now widely recognized. T helper 17 cells are the dominant effector T cell involved in the induction of autoimmune chronic diseases by production of several proinflamatory cytokines especially interleukin -17. T helper 17 cells present in the joint may create a positive feedback loop leading to the continuous activation of T cells, which is a critical event in the generation of autoimmunity.

Nuclear hormone retinoic acid receptor-related orphan receptor variant 2, encoded by RORC2 gene located on chromosome 1q21-q23 is a master transcriptional factor that can drive T helper 17 cells differentiation. It is now well established that for T helper 17 cells differentiation, it is critical to have transforming growth factor β1 in the presence of interleukin-1, interleukin -6, or interleukin -21 to decrease suppressive FoxP3 and upregulate RORC2 gene encoded unique lineage-specific transcription factor, nuclear hormone retinoic acid receptor-related orphan receptor variant 2.

Knockdown of transcription factor nuclear hormone retinoic acid receptor-related orphan receptor variant 2 cause high forkhead transcriptional repressor levels and reduces expression of pro-inflammatory cytokines such as interleukin-1, interleukin -6, interleukin -17 and transforming growth factor β1 suggesting that the role of nuclear hormone retinoic acid receptor-related orphan receptor variant 2 in T helper 17 cells differentiation involves not only in induction of T helper 17 cells characteristics genes, but also suppression of Treg cells specific programs that play an important role in immunological tolerance.

Single nucleotide polymorphisms underlie differences in our susceptibility to disease, the severity of illness and the way our body responds to pathogens, chemicals, drugs, vaccines and other agents. For example, a single base mutation in the apolipoprotein E gene is associated with a higher risk for Alzheimer's disease.

RORC2 gene may represent a candidate gene for autoimmune diseases. However, not too much is known about the function of RORC2 genetic polymorphisms in autoimmune diseases, including rheumatoid arthritis. The RORC2 gene polymorphisms have been analyzed in a Behcet's disease, secondary lymphedema and type 2 diabetes mellitus and rheumatoid arthritis in a study on Polish population.

This is why analysis of polymorphisms within the RORC2 gene together with estimation of nuclear hormone retinoic acid receptor-related orphan receptor variant 2 serum levels may help to uncover their correlations with some clinical and laboratory findings in rheumatoid arthritis.

Conditions

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Genetic Predisposition to Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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Rheumatoid arthritis patients

A total of 55 rheumatoid arthritis patients diagnosed according to 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria recruited from Clinical Rheumatology unit, Internal Medicine, Assiut University Hospitals

No interventions assigned to this group

controls

A total of 33 age and sex matched healthy controls randomly selected from healthy volunteers

No interventions assigned to this group

Eligibility Criteria

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Exclusion Criteria

1. Patients with other connective tissue diseases \[e.g. systemic lupus erythematosis , systemic sclerosis, Behcet's disease,…etc\]
2. Patients with other autoimmune diseases,
3. Patients with genetic diseases were excluded from the study
4. Patients with chronic liver or kidney diseases, . -
Minimum Eligible Age

20 Years

Maximum Eligible Age

73 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Fatma Sayed

principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Khaled M Hassanein, Professor

Role: STUDY_DIRECTOR

Assiut University

References

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Ikeda S, Saijo S, Murayama MA, Shimizu K, Akitsu A, Iwakura Y. Excess IL-1 signaling enhances the development of Th17 cells by downregulating TGF-beta-induced Foxp3 expression. J Immunol. 2014 Feb 15;192(4):1449-58. doi: 10.4049/jimmunol.1300387. Epub 2014 Jan 15.

Reference Type BACKGROUND
PMID: 24431229 (View on PubMed)

Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001 Sep 15;358(9285):903-11. doi: 10.1016/S0140-6736(01)06075-5.

Reference Type BACKGROUND
PMID: 11567728 (View on PubMed)

Liao D, Hou S, Zhang J, Fang J, Liu Y, Bai L, Cao Q, Kijlstra A, Yang P. Copy number variants and genetic polymorphisms in TBX21, GATA3, Rorc, Foxp3 and susceptibility to Behcet's disease and Vogt-Koyanagi-Harada syndrome. Sci Rep. 2015 Apr 15;5:9511. doi: 10.1038/srep09511.

Reference Type BACKGROUND
PMID: 25873156 (View on PubMed)

Lim HW, Kang SG, Ryu JK, Schilling B, Fei M, Lee IS, Kehasse A, Shirakawa K, Yokoyama M, Schnolzer M, Kasler HG, Kwon HS, Gibson BW, Sato H, Akassoglou K, Xiao C, Littman DR, Ott M, Verdin E. SIRT1 deacetylates RORgammat and enhances Th17 cell generation. J Exp Med. 2015 May 4;212(5):607-17. doi: 10.1084/jem.20132378. Epub 2015 Apr 27.

Reference Type BACKGROUND
PMID: 25918343 (View on PubMed)

Liu HP, Cao AT, Feng T, Li Q, Zhang W, Yao S, Dann SM, Elson CO, Cong Y. TGF-beta converts Th1 cells into Th17 cells through stimulation of Runx1 expression. Eur J Immunol. 2015 Apr;45(4):1010-8. doi: 10.1002/eji.201444726. Epub 2015 Feb 11.

Reference Type BACKGROUND
PMID: 25605286 (View on PubMed)

Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008 Jun;223:87-113. doi: 10.1111/j.1600-065X.2008.00628.x.

Reference Type BACKGROUND
PMID: 18613831 (View on PubMed)

Wolf AB, Caselli RJ, Reiman EM, Valla J. APOE and neuroenergetics: an emerging paradigm in Alzheimer's disease. Neurobiol Aging. 2013 Apr;34(4):1007-17. doi: 10.1016/j.neurobiolaging.2012.10.011. Epub 2012 Nov 16.

Reference Type BACKGROUND
PMID: 23159550 (View on PubMed)

Paradowska-Gorycka A, Stypinska B, Pawlik A, Romanowska-Prochnicka K, Haladyj E, Manczak M, Olesinska M. RORC2 Genetic Variants and Serum Levels in Patients with Rheumatoid Arthritis. Int J Mol Sci. 2016 Apr 1;17(4):488. doi: 10.3390/ijms17040488.

Reference Type BACKGROUND
PMID: 27043554 (View on PubMed)

Other Identifiers

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GPRA

Identifier Type: -

Identifier Source: org_study_id

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