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Association between adult-onset Still's disease and interleukin-18 gene polymorphisms

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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.

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Acknowledgements

Supported by a grant from the Research for the Future Program of the Japan Society for the Promotion of Science and a Grant-in-Aid from the Tokyo Biochemical Research Foundation.

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Authors and Affiliations

  1. Institute of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan

    T Sugiura, Y Kawaguchi, M Harigai, H Terajima-Ichida, Y Kitamura, T Furuya, N Ichikawa, S Kotake, M Tanaka, M Hara & N Kamatani

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  1. T Sugiura
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  2. Y Kawaguchi
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  3. M Harigai
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  4. H Terajima-Ichida
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  5. Y Kitamura
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  6. T Furuya
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  7. N Ichikawa
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  8. S Kotake
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  9. M Tanaka
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  10. M Hara
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  11. N Kamatani
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Correspondence to Y Kawaguchi.

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Sugiura, T., Kawaguchi, Y., Harigai, M. et al. Association between adult-onset Still's disease and interleukin-18 gene polymorphisms. Genes Immun 3, 394–399 (2002). https://doi.org/10.1038/sj.gene.6363922

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  • DOI: https://doi.org/10.1038/sj.gene.6363922

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