Association Between Adult-Onset Still's Disease and interleukin-18 Gene Polymorphisms

Genes Immun. 2002 Nov;3(7):394-9. doi: 10.1038/sj.gene.6363922.


Recently, we reported that serum concentration of IL-18 is strikingly high in patients with adult-onset Still's disease (AOSD). The aim of the present study was to screen for genetic polymorphisms in the human IL-18 (hIL-18) gene and to determine the association of polymorphisms with susceptibility to AOSD. We investigated the 6.7 kb region upstream of exon 2 of hIL-18 gene, in which a promoter activity had been reported. Sixteen AOSD patients, 144 rheumatoid arthritis (RA) patients and 92 healthy control individuals were studied. We found seven single nucleotide polymorphisms and a single 9 bp insertion which were frequently present in the AOSD patients. Three haplotypes including a unique combination of these polymorphisms were also determined. Of them, haplotype S01 contained all eight of these polymorphisms. The frequency of individuals carrying a diplotype configuration, ie a combination of two haplotypes, of S01/S01 was significantly higher in the AOSD patients than in the healthy controls (P=0.00059, Fischer's exact probability test, odds ratio [OR]=7.81, 95% confidence interval [95% CI]=2.48-24.65) and the RA patients (P=0.015, Fischer's exact probability test, OR=4.0, 95% CI=1.39-11.54). We therefore conclude that possession of the diplotype configuration of S01/S01 is a major genetic risk factor for susceptibility to AOSD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Interleukin-18 / genetics*
  • Introns
  • Male
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Still's Disease, Adult-Onset / genetics*


  • Interleukin-18