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A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes

Genes & Immunity volume 10, pages 120–124 (2009)Cite this article

Abstract

Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider spectrum of autoimmune diseases. Investigating large patient cohorts from six different autoimmune diseases, that is autoimmune Addison's disease (n=333), type 1 diabetes (n=1086), multiple sclerosis (n=502), rheumatoid arthritis (n=945), systemic lupus erythematosus (n=156) and juvenile idiopathic arthritis (n=505), against 3273 healthy controls, we analyzed four single nucleotide polymorphisms (SNPs) in NALP1. The major allele of the coding SNP rs12150220 revealed significant association with autoimmune Addison's disease compared with controls (OR=1.25, 95% CI: 1.06–1.49, P=0.007), and with type 1 diabetes (OR=1.15, 95% CI: 1.04–1.27, P=0.005). Trends toward the same associations were seen in rheumatoid arthritis, systemic lupus erythematosus and, although less obvious, multiple sclerosis. Patients with juvenile idiopathic arthritis did not show association with NALP1 gene variants. The results indicate that NALP1 and the innate immune system may be implicated in the pathogenesis of many autoimmune disorders, particularly organ-specific autoimmune diseases.

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Acknowledgements

We are indebted to each patient and the Norwegian Bone Marrow Registry for contributing with DNA samples for healthy controls, and The Norwegian Study Group for Childhood Diabetes for collection of type 1 diabetes samples. Vibeke Lilleby and Inge M Gilboe are thanked for collecting the lupus samples. Berit Flatø and Anne Marit Selvaag, Rikshospitalet-Radiumhospitalet Medical Centre, are acknowledged for collecting the juvenile idiopathic arthritis samples. Furthermore, we thank Siri Flåm, Rikshospitalet, Sigrid Erdal, Haukeland University Hospital, and Alice Stormyr and Hanne Akselsen, Ullevål University Hospital, for help with genotyping. The study was supported by grants from The Seventh Framework Programme ‘Euradrenal,’ The Western and South-Eastern Regional Health Authorities, the Norwegian Research Council and the University of Bergen.

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Author notes

  1. P M Knappskog and E S Husebye: These authors contributed equally to this work.

Authors and Affiliations

  1. Centre of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

    N F Magitta, A S Bøe Wolff, S Johansson & P M Knappskog

  2. Institute of Clinical Medicine, University of Bergen, Bergen, Norway

    N F Magitta, S Johansson, K-M Myhr, P R Njølstad & P M Knappskog

  3. Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

    N F Magitta

  4. Department of Medicine, Haukeland University Hospital, Bergen, Norway

    A S Bøe Wolff & E S Husebye

  5. Institute of Medicine, University of Bergen, Bergen, Norway

    A S Bøe Wolff & E S Husebye

  6. Institute of Biomedicine, University of Bergen, Bergen, Norway

    S Johansson

  7. Institute of Medical Genetics, University of Oslo, Oslo, Norway

    B Skinningsrud & D E Undlien

  8. Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway

    B Skinningsrud & D E Undlien

  9. Institute of Immunology, Rikshospitalet-Radiumhospitalet University Hospital, Oslo, Norway

    B A Lie

  10. Department of Neurology, Haukeland University Hospital, Bergen, Norway

    K-M Myhr

  11. Department of Paediatrics, Ullevål University Hospital, Oslo, Norway

    G Joner

  12. Institute of Health Management and Health Economics, University of Oslo, Oslo, Norway

    G Joner

  13. Department of Paediatrics, Haukeland University Hospital, Bergen, Norway

    P R Njølstad

  14. Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway

    T K Kvien

  15. Department of Rheumatology, Rikshospitalet-Radiumhospitalet University Hospital, Oslo, Norway

    Ø Førre

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  1. N F Magitta
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  5. B A Lie
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Corresponding author

Correspondence to E S Husebye.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Magitta, N., Bøe Wolff, A., Johansson, S. et al. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes. Genes Immun 10, 120–124 (2009). https://doi.org/10.1038/gene.2008.85

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