An overview on the genetic of rheumatoid arthritis: a never-ending story

Autoimmun Rev. 2011 Aug;10(10):599-608. doi: 10.1016/j.autrev.2011.04.021. Epub 2011 Apr 22.


Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, multi-factorial disease sustained by environmental and genetic factors. These seem to be necessary but not sufficient in the disease development, nonetheless they can be responsible of different clinical pictures and response to therapy, and they can represent potential therapeutic targets. Several genes have been indicated so far in the pathogenesis of RA. The most important region is the Human Leukocyte Antigen (HLA) that contributes to approximately half of the genetic susceptibility for RA. The association seems to be stronger or specific for anti-citrullinated protein antibodies positive disease. Several alleles in the epitope-recognition part of the HLA molecule that show the highest association with RA susceptibility, also share a common string of amminoacid residues (the so-called shared-epitope hypothesis). Other variants in potentially pathogenic genes located in non-MHC regions have been implicated by recently performed genome wide analysis studies. These genes include PTPN22, TRAF1-C5, PADI4, STAT4. Other polymorphisms seem to be responsible for more aggressive disease phenotype such as those located at TNF, IL-1, IL-6, IL-4, IL-5, OPN, PRF1. However, still nowadays, the genetic background of RA remains to be clearly depicted, and the efforts in the post-genomic era can bring to an estimation of the real likelihood of the genetic effect on RA. Finally, the discovery of new genes associated with the disease can be relevant in finding potential biomarkers, potentially useful in disease diagnosis and treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Cytokines / genetics
  • Genetic Markers
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics*
  • Humans
  • Hydrolases / genetics
  • Pathology, Molecular
  • Polymorphism, Genetic
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics*
  • Protein-Arginine Deiminase Type 4
  • Protein-Arginine Deiminases
  • Receptors, IgG / genetics


  • Cytokines
  • Genetic Markers
  • HLA Antigens
  • Receptors, IgG
  • Hydrolases
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • PADI4 protein, human
  • Protein-Arginine Deiminase Type 4
  • Protein-Arginine Deiminases