Interleukin-1 receptor antagonist gene polymorphisms are associated with disease severity in Black South Africans with rheumatoid arthritis

Joint Bone Spine. 2008 Jul;75(4):422-5. doi: 10.1016/j.jbspin.2007.09.015. Epub 2008 May 12.


Objective: To test for genetic associations between polymorphisms of the interleukin-1 (IL-1) gene cluster and disease susceptibility and severity in Black South Africans with rheumatoid arthritis (RA).

Methods: Allele and genotype frequencies of IL1B (-511) and (+3954) and IL1RN variable number of tandem repeat (VNTR) and (+2018) were compared between 141 RA patients and 101 healthy controls.

Results: No significant differences in allelic distribution at the four loci were observed between RA patients and controls. Within the RA group, the IL1RN*2 (two repeats of an 86bp tandem repeat) at the IL1RN VNTR locus was independently associated with higher Larsen radiologic damage scores (LDS), corrected for disease duration (p=0.04). Moreover, the inferred haplotype, consisting of IL1RN*2 and (+2018) 'C' allele, was associated with significantly higher LDS, on average 15 points higher, compared to the base haplotype of IL1RN*long (three or more repeats) and (+2018) 'T' allele (p=0.009). The common IL1B (-511) 'T' allele was associated with a poorer modified health assessment questionnaire disability index (p=0.02).

Conclusion: Our findings provide further evidence of a possible role of polymorphisms of the IL-1 gene cluster in disease severity in RA, and particularly IL1RN*2 as a marker of erosive joint damage in Black South Africans with RA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / ethnology*
  • Arthritis, Rheumatoid / genetics*
  • Black People
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / genetics*
  • Interleukin-1beta
  • Male
  • Polymorphism, Genetic*
  • Severity of Illness Index
  • South Africa / epidemiology
  • Tandem Repeat Sequences


  • IL1B protein, human
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta