Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and rheumatoid arthritis in Japanese patients, and maximum-likelihood estimation of combinatorial effect that two genetic loci have on susceptibility to the disease

Am J Hum Genet. 2001 Mar;68(3):674-85. doi: 10.1086/318789. Epub 2001 Feb 14.


Genetic variants of interleukin-3 (IL-3), a well-studied cytokine, may have a role in the pathophysiology of rheumatoid arthritis (RA); but reports on this association sometimes conflict. A case-control study was designed to investigate association between RA and a single-nucleotide polymorphism (SNP) in the IL-3 promoter region. Comparison of cases of RA versus control individuals yielded a chi(2) value of 14.28 (P=.0002), with a genotype odds ratio of 2.24 (95% confidence interval [95%CI] 1.44-3.49). When female cases with earlier onset were compared with female control individuals, the SNP revealed an even more significant correlation, with chi2=21.75 (P=.000004) and a genotype odds ratio of 7.27 (95%CI 2.80-18.89). The stronger association that we observed in this clinically distinct subgroup (females with early onset), within a region where linkage disequilibrium was not significantly extended, suggested that the genuine RA locus should locate either within or close to the IL-3 gene. Combined genotype data on SNPs on eight other candidate genes were combined with our IL-3 results, to estimate relationships between pairs of loci and RA, by maximum-likelihood analysis. The utility of combining the genotype data in this way to identify possible contributions of various genes to this disease is discussed.

Publication types

  • Comparative Study

MeSH terms

  • Age of Onset
  • Arthritis, Rheumatoid / genetics*
  • Asian Continental Ancestry Group / genetics
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • Interleukin-3 / genetics*
  • Japan
  • Likelihood Functions
  • Male
  • Middle Aged
  • Models, Statistical
  • Molecular Sequence Data
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic*
  • Reference Values


  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Interleukin-3