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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 3/2006

Open Access 01-06-2006 | Research article

A promoter haplotype of the interleukin-18gene is associated with juvenile idiopathic arthritis in the Japanese population

Authors: Tomoko Sugiura, Nobuaki Maeno, Yasushi Kawaguchi, Syuji Takei, Hiroyuki Imanaka, Yoshifumi Kawano, Hisae Terajima-Ichida, Masako Hara, Naoyuki Kamatani

Published in: Arthritis Research & Therapy | Issue 3/2006

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Abstract

Recently, we reported that genetic polymorphisms within the human IL18 gene were associated with disease susceptibility to adult-onset Still's disease (AOSD), which is characterized by extraordinarily high serum levels of IL-18. Because high serum IL-18 induction has also been observed in the systemic type of juvenile idiopathic arthritis (JIA), we investigated whether similar genetic skewing is present in this disease. Three haplotypes, S01, S02, and S03, composed of 13 genetic polymorphisms covering two distinct promoter regions, were determined for 33 JIA patients, including 17 with systemic JIA, 10 with polyarthritis, and 6 with oligoarthritis. Haplotypes were also analyzed for 28 AOSD patients, 164 rheumatoid arthritis (RA) patients, 102 patients with collagen diseases, and 173 healthy control subjects. The frequency of individuals carrying a diplotype configuration (a combination of two haplotypes) of S01/S01 was significantly higher in the JIA patients, including all subgroups, than in the healthy controls (P = 0.0045, Fischer exact probability test; odds ratio (OR) = 3.55, 95% confidence interval (CI) = 1.55–8.14). In patients with systemic JIA, its frequency did not differ statistically from that of normal controls. Nevertheless, it is possible that haplotype S01 is associated with the phenotype of high IL-18 production in systemic JIA because the patients carrying S01/S01 showed significantly higher serum IL-18 levels compared with patients with other diplotype configurations (P = 0.017, Mann-Whitney U test). We confirmed that the frequency of the diplotype configuration of S01/S01 was significantly higher in AOSD patients than in healthy control subjects (P = 0.011, OR = 3.45, 95% CI = 1.42–8.36). Furthermore, the RA patients were also more predisposed to have S01/S01 (P = 0.018, OR = 2.00, 95% CI = 1.14–3.50) than the healthy control subjects, whereas the patients with collagen diseases did not. In summary, the diplotype configuration of S01/S01 was associated with susceptibility to JIA as well as AOSD and RA, and linked to significantly higher IL-18 production in systemic JIA. Possession of the diplotype configuration of S01/S01 would be one of the genetic risk factors for susceptibility to arthritis in the Japanese population.
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Metadata
Title
A promoter haplotype of the interleukin-18gene is associated with juvenile idiopathic arthritis in the Japanese population
Authors
Tomoko Sugiura
Nobuaki Maeno
Yasushi Kawaguchi
Syuji Takei
Hiroyuki Imanaka
Yoshifumi Kawano
Hisae Terajima-Ichida
Masako Hara
Naoyuki Kamatani
Publication date
01-06-2006
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 3/2006
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar1930

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