title: Association between adult-onset Still's disease and interleukin-18 gene polymorphisms.
abstract: 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.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sugiura
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: M
authors.initials: M
authors.lastname: Harigai
authors.forename: H
authors.initials: H
authors.lastname: Terajima-Ichida
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Furuya
authors.forename: N
authors.initials: N
authors.lastname: Ichikawa
authors.forename: S
authors.initials: S
authors.lastname: Kotake
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Hara
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D007438:Introns; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016706:Still's Disease, Adult-Onset / Q000235:genetics*
chemical_list: D020382:Interleukin-18