Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis

Arthritis Rheum. 1999 Jun;42(6):1093-100. doi: 10.1002/1529-0131(199906)42:6<1093::AID-ANR5>3.0.CO;2-P.


Objective: To test if interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-4, or IL-10 gene polymorphisms could be used as markers of susceptibility or severity in rheumatoid arthritis (RA).

Methods: The study included 108 patients with early RA followed up for 2 years and 128 healthy controls. From genomic DNA, 6 polymorphisms in genes for IL-1beta, IL-1Ra, IL-10, and IL-4 were typed. Allelic frequencies and carriage rates were compared between RA patients and controls, between patients with erosive and nonerosive RA, and between patients with or without sustained remission.

Results: The RP1 allele of the IL-4 gene was found with a significantly higher frequency in RA patients compared with controls. The combination of an RA-related HLA-DR allele expressing shared epitope and the presence of allele E2 in IL-1beta exon 5 was found to expose patients to an increased risk of erosive disease, with an odds ratio of 8.20 (95% confidence interval 2.59-25.84, P < 0.0001). No significant association was observed between polymorphisms and the occurrence of sustained remission.

Conclusion: This report, for the first time, indicates an association between RA and a polymorphic IL-4 gene sequence located in 5q31-33. In addition, the results show the prognostic value of a polymorphism in IL-1beta exon 5, which allowed prediction of erosive disease with a specificity of 91.8% in 42.1% of patients. Although these observations are very interesting, they have to be considered preliminary and will need to be confirmed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / physiopathology
  • DNA / analysis
  • DNA Primers / chemistry
  • Disease Susceptibility
  • Gene Frequency
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Histocompatibility Testing
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / genetics*
  • Interleukin-10 / genetics*
  • Interleukin-4 / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Severity of Illness Index
  • Sialoglycoproteins / genetics*


  • DNA Primers
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Sialoglycoproteins
  • Interleukin-10
  • Interleukin-4
  • DNA