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Allelic variants in genes associated with hereditary periodic fever syndromes as susceptibility factors for reactive systemic AA amyloidosis

Genes & Immunity volume 5, pages 289–293 (2004)Cite this article

Abstract

We investigated the hypothesis that low-penetrance mutations in genes (TNFRSF1A, MEFV and NALP3/CIAS1) associated with hereditary periodic fever syndromes (HPFs) might be risk factors for AA amyloidosis among patients with chronic inflammatory disorders, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), Crohn's disease, undiagnosed recurrent fevers and HPFs themselves. Four of 67 patients with RA plus amyloidosis had MEFV variants compared with none of 34 RA patients without amyloid (P value=0.03). The E148Q variant of MEFV was present in two of the three patients with TNF receptor-associated periodic syndrome (TRAPS) complicated by amyloid in two separate multiplex TRAPS families containing 5 and 16 affected members respectively, and the single patient with Muckle–Wells syndrome who had amyloidosis was homozygous for this variant. The R92Q variant of TNFRSF1A was present in two of 61 JIA patients with amyloidosis, and none of 31 nonamyloidotic JIA patients. No HPF gene mutations were found in 130 healthy control subjects. Although allelic variants in HPFs genes are not major susceptibility factors for AA amyloidosis in chronic inflammatory disease, low-penetrance variants of MEFV and TNFRSF1A may have clinically significant proinflammatory effects.

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Acknowledgements

We are particularly grateful to the patients who agreed to participate in the study. This work was supported in part by the Special Trustees of Barts and the London Joint Research Board and the Wellcome Trust (to MMcD), The Finska Lakaresallskapet (TP) and the Research Funds of Helsinki University Hospital (AR, TP), the Medical Research Council, UK (to PNH).

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Authors and Affiliations

  1. Department of Diabetes and Metabolic Medicine, Unit of Molecular Medicine, Barts and London, Queen Mary's School of Medicine and Dentistry, Whitechapel, London, UK

    E Aganna, G A Hitman & M F McDermott

  2. Department of Medicine, Centre for Amyloidosis and Acute Phase Proteins, RFUCMS, Royal Free Hospital, London, UK

    P N Hawkins, A Bybee & H J Lachmann

  3. Department of Paediatrics, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey

    S Ozen, A Bakkaloglu, N Besbas & R Topaloglu

  4. Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

    T Pettersson

  5. Department of Medical Genetics, Belfast City Hospital, Northern Ireland

    S A McKee

  6. Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland

    L Karenko & A Ranki

  7. Division of Rheumatology, Allergy, and Immunology, University of California at San Diego, USA

    H M Hoffman

  8. Centre of Paediatric and Adolescent Rheumatology, Windeyer Institute of Medical Sciences, University College London, UK

    P Woo

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  1. E Aganna
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  2. P N Hawkins
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  8. L Karenko
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  9. A Ranki
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  12. R Topaloglu
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  13. H M Hoffman
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  14. G A Hitman
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  16. M F McDermott
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Corresponding author

Correspondence to M F McDermott.

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Electronic-Database Information

URLs for data in this article are as follows:

Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim (for FCU/FCAS [MIM 120100], FHF [MIM 142680], FMF [MIM 249100], HIDS [MIM 260920], and MWS [MIM 191900])

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Aganna, E., Hawkins, P., Ozen, S. et al. Allelic variants in genes associated with hereditary periodic fever syndromes as susceptibility factors for reactive systemic AA amyloidosis. Genes Immun 5, 289–293 (2004). https://doi.org/10.1038/sj.gene.6364070

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  • DOI: https://doi.org/10.1038/sj.gene.6364070

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