Association of the interleukin-1 gene cluster on chromosome 2q13 with knee osteoarthritis

Arthritis Rheum. 2002 Jun;46(6):1519-27. doi: 10.1002/art.10260.


Objective: To investigate whether the interleukin-1 (IL-1) ligand gene cluster at 2q13 encodes for genetic susceptibility to primary osteoarthritis (OA).

Methods: Seven single-nucleotide polymorphisms (SNPs) and a variable-number tandem repeat (VNTR) polymorphism from within the IL-1 ligand genes IL1A, IL1B, and IL1RN were genotyped in a cohort of 557 OA cases and 557 age-matched controls.

Results: None of the variants demonstrated association in the unstratified data set. However, when cases were stratified according to sex and site of disease (hip or knee), 4 SNPs showed marginal evidence for association (P < 0.1) in knee cases (n = 136) and male knee cases (n = 58). For 2 of these SNPs, evidence for association was enhanced when probands from 60 knee-only affected sibling pair families were genotyped and combined with the original knee cases (P < or = 0.05). Further analysis revealed that the associated alleles at 2 of these SNPs were markers for the same haplotype, the frequency of which was significantly elevated when knee cases and knee probands were combined (P = 0.01, odds ratio [OR] 1.4) and when male knee cases and male knee probands were combined (P = 0.009, OR 1.7). Furthermore, linkage analysis of 2q revealed suggestive evidence for linkage to the IL-1 gene clusters in affected sibling pairs concordant for knee OA but no evidence for linkage in affected sibling pairs concordant for hip OA.

Conclusion: The IL-1 ligand cluster encodes for susceptibility to knee OA but not to hip OA, highlighting the genetic heterogeneity of this common, complex disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Chromosomes, Human, Pair 2*
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / genetics*
  • Male
  • Middle Aged
  • Osteoarthritis, Hip / genetics
  • Osteoarthritis, Knee / genetics*
  • Polymorphism, Single Nucleotide
  • Sialoglycoproteins / genetics*


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Sialoglycoproteins