Genetic Predisposition to DiseaseNCT03615729
RORC Genetic Polymorphism of Rheumatoid Arthritis
An observational study of Genetic Predisposition to Disease, run by Assiut University.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 73 yearsHealthy volunteers can take part
- Conditions the study is for
- Genetic Predisposition to Disease
- How many people
- 89 participants
- Where
- No sites listed yet
- Study dates
- 30 Jun 2016to 30 Jun 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 73 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: A total of 55 patients (with rheumatoid arthritis diagnosed according to 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria) were recruited from Clinical Rheumatology unit, Internal Medicine, Assiut University Hospitals and 34 healthy volunteers were included in the study. Age of both of patients and healthy controls are 45.13 ± 10.6 years with a median age 45 years (20-73 years) and 43.00 ± 11.1 years with a median age 43 years (20-65 years) respectively. The numbers of females and males in RA patients are 50 and 5, respectively, and those in controls are 31 and 3 respectively.
Who may be able to join
None listed.
Who cannot join
- Patients with other connective tissue diseases [e.g. systemic lupus erythematosis , systemic sclerosis, Behcet's disease,…etc]
- Patients with other autoimmune diseases,
- Patients with genetic diseases were excluded from the study
- Patients with chronic liver or kidney diseases, . -
About this study
Official title: RORC Genetic Polymorphism and Serum Levels in Patients With Rheumatoid Arthritis
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.
Read the 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.
- Conditions
- Genetic Predisposition to Disease
- Keywords
- Rheumatoid arthritis, Genetic polymorphism, RORc2 protein, T helper 17
- Medical subject headings
- Genetic Predisposition to Disease, Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 | |
| controls | A total of 33 age and sex matched healthy controls randomly selected from healthy volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of SNPs genetic polymorphisms in RORC gene in rheumatoid arthritis
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
Measured: 2 hours
Secondary outcomes (1)
Determination of serum Levels of RORc2
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
Measured: 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2018
- Study start30 Jun 2016
- Primary completion30 Mar 2018
- Study completion30 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Genetic Predisposition to DiseaseStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fatma Sayed, Assiut University
- Investigators
- Khaled M Hassanein, Professor, Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03615729
- Sponsor's protocol ID
- GPRA
- Status last verified
- Jul 2018
- First submitted
- 22 Jul 2018
- Last updated
- 6 Aug 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24431229Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001 Sep 15;358(9285):903-11. doi: 10.1016/S0140-6736(01)06075-5.
PubMed 11567728Liao 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.
PubMed 25873156Lim 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.
PubMed 25918343Liu 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.
PubMed 25605286Tesmer 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.
PubMed 18613831Wolf 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.
PubMed 23159550Paradowska-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.
PubMed 27043554
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RORC Genetic Polymorphism and Serum Levels in Patients With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT03615729
- Acronym / sponsor ID
- GPRA
- Conditions
- Genetic Predisposition to Disease
- Keywords
- Rheumatoid arthritis, Genetic polymorphism, RORc2 protein, T helper 17
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 30 Jun 2016 (actual)
- Primary completion
- 30 Mar 2018 (actual)
- Study completion
- 30 Jun 2018 (actual)
- First posted
- 6 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
| controls | – | –A total of 33 age and sex matched healthy controls randomly selected from healthy volunteers |
Who may qualify
- Ages
- 20 to 73 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- A total of 55 patients (with rheumatoid arthritis diagnosed according to 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria) were recruited from Clinical Rheumatology unit, Internal Medicine, Assiut University Hospitals and 34 healthy volunteers were included in the study. Age of both of patients and healthy controls are 45.13 ± 10.6 years with a median age 45 years (20-73 years) and 43.00 ± 11.1 years with a median age 43 years (20-65 years) respectively. The numbers of females and males in RA patients are 50 and 5, respectively, and those in controls are 31 and 3 respectively.
Key inclusion criteria (0 listed)
Key exclusion criteria (4 listed)
- Patients with other connective tissue diseases [e.g. systemic lupus erythematosis , systemic sclerosis, Behcet's disease,…etc]
- Patients with other autoimmune diseases,
- Patients with genetic diseases were excluded from the study
- Patients with chronic liver or kidney diseases, . -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Detection of SNPs genetic polymorphisms in RORC gene in rheumatoid arthritis
Time frame: 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
1 secondary outcome
Determination of serum Levels of RORc2
Time frame: 3 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2018.
- Background: PubMed 24431229Ikeda 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.
- Background: PubMed 11567728Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001 Sep 15;358(9285):903-11. doi: 10.1016/S0140-6736(01)06075-5.
- Background: PubMed 25873156Liao 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.
- Background: PubMed 25918343Lim 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.
- Background: PubMed 25605286Liu 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.
- Background: PubMed 18613831Tesmer 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.
- Background: PubMed 23159550Wolf 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.
- Background: PubMed 27043554Paradowska-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Khaled M Hassanein, Professor study director
Assiut University
Questions about this trial
What is this clinical trial studying?
An observational study of Genetic Predisposition to Disease, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detection of SNPs genetic polymorphisms in RORC gene in rheumatoid arthritis (time frame: 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03615729, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2018.