RORC Genetic Polymorphism of Rheumatoid Arthritis
Condition: Genetic Predisposition to Disease
MeSH terms: Arthritis; Arthritis, Rheumatoid; Genetic Predisposition to Disease
Study type: Observational

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.
    

Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Probability Sample
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.
      
Biospecimen description: 
      A total of 10 ml whole blood samples were obtained and were divided into two tubes; EDTA tube
      for genomic DNA extraction and serum-separating tubes for retinoic acid receptor-related
      orphan receptor variant 2 serum level determination by enzyme linked immunosorbant assay
    
Keywords: Rheumatoid arthritis; Genetic polymorphism; RORc2 protein; T helper 17