RORC Genetic Polymorphism of Rheumatoid Arthritis

Completed

• Conditions: Genetic Predisposition to Disease

• Registration Number: NCT03615729
• Lead Sponsor: Assiut University

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-06-30
• Primary Completion: 2018-03-30
• Study Completion: 2018-06-30
• Status Verified: 2018-07
• Study First Submitted: 2018-07-22
• Study First Submitted QC: 2018-07-31
• Last Update Submitted: 2018-07-31
• Study First Posted: 2018-08-06
• Last Update Posted: 2018-08-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 89

Inclusion Criteria

• patients with rheumatoid arthritis diagnosed according to 2010 ACR / EULAR Rheumatoid Arthritis Classification 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, . -

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Detection of SNPs genetic polymorphisms in RORC gene in rheumatoid arthritis	2 hours	Taqman SNP genotyping of rs9826 A/G, rs3790515 C/T and rs3828057 C/T in rheumatoid arthritis patients and control group to detect any possible association between RORC genetic polymorphism and rheumatoid arthritis

Secondary Outcome Measures

Name	Time	Method
Determination of serum Levels of RORc2	3 hours	Determination of serum Levels of RORc2 were determined by enzyme-linked immunosorbent assay in rheumatoid arthritis patient and controls to determine RORc2 association with the risk and severity of the disease