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Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis

Genes & Immunity volume 9, pages 349–357 (2008)Cite this article

Abstract

Patients with systemic juvenile idiopathic arthritis (sJIA) have a characteristic daily spiking fever and elevated levels of inflammatory cytokines. Members of the interleukin-1 (IL-1) gene family have been implicated in various inflammatory and autoimmune diseases, and treatment with the IL-1 receptor antagonist, Anakinra, shows remarkable improvement in some patients. This work describes the most comprehensive investigation to date of the involvement of the IL-1 gene family in sJIA. A two-stage case–control association study was performed to investigate the two clusters of IL-1 family genes using a tagging single nucleotide polymorphism (SNP) approach. Genotyping data of 130 sJIA patients and 151 controls from stage 1 highlighted eight SNPs in the IL1 ligand cluster region and two SNPs in the IL1 receptor cluster region as showing a significant frequency difference between the populations. These 10 SNPs were typed in an additional 105 sJIA patients and 184 controls in stage 2. Meta-analysis of the genotypes from both stages showed that three IL1 ligand cluster SNPs (rs6712572, rs2071374 and rs1688075) and one IL1 receptor cluster SNP (rs12712122) show evidence of significant association with sJIA. These results indicate that there may be aberrant control of the activity of the IL-1 family in sJIA patients causing the increased susceptibility to the disease.

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Acknowledgements

We thank BSPAR study group members: Dr M Abinun, Dr M Becker, Dr A Bell, Professor A Craft, Dr E Crawley, Dr J David, Dr H Foster, Dr J Gardener-Medwin, Dr J Griffin, Dr A Hall, Dr M Hall, Dr A Herrick, Dr P Hollingworth, Dr L Holt, Dr S Jones, Dr G Pountain, Dr C Ryder, Professor T Southwood, Dr I Stewart, Dr H Venning, Dr L Wedderburn, Professor P Woo and Dr S Wyatt; Dr AM Prieur and the French association Kourir; Dr J Packham, for the contribution of patient DNA and Dr Ele Zeggini for assistance with analysis. This work was funded by the Nuffield Foundation Oliver Bird Rheumatism Program and the Arthritis Research Campaign (arc).

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Authors and Affiliations

  1. Centre for Paediatric and Adolescent Rheumatology, Windeyer Institute for Medical Sciences, University College London, London, UK

    C J W Stock, E M Ogilvie, J M Samuel, M Fife & P Woo

  2. Guy's, Kings and St Thomas' School of Medicine, London, UK

    C M Lewis

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  2. E M Ogilvie
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Correspondence to P Woo.

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Stock, C., Ogilvie, E., Samuel, J. et al. Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis. Genes Immun 9, 349–357 (2008). https://doi.org/10.1038/gene.2008.24

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