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Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjögren's syndrome

Genes & Immunity volume 10, pages 68–76 (2009)Cite this article

Abstract

Primary Sjögren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) >1.4 and P-values <0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P=2.5 × 10−9. The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.

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Acknowledgements

Genotyping of the SNPs was performed by the SNP Technology Platform in Uppsala, established by funding from the Knut and Alice Wallenberg Foundation. This study was supported by the Swedish Research Council for Medicine (A-CS, LR), the Swedish Rheumatism Association (LR, ET), the King Gustaf V 80-year Foundation (LR), Ulla and Roland Gustafsson Foundation (LR) and the Strategic Research Program at Helse Bergen, Helse Vest and the Broegelmann Foundation (JGB, RJ). GN has received a postdoctoral grant from Astrid Karlsson Foundation, ET has received a postdoctoral grant from Anna-Greta Crafoord Foundation and from the Malmö University Hospital Cancer Foundation. We thank Snaevar Sigurdsson for genotyping the 563 Swedish controls, Anders Lundmark for help with statistical analysis, and Rezvan Kiani, Linda Öjkvist, Hawa Camara, Käth Nilsson and Raul Figueroa for collecting patient samples.

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Author notes

  1. G Nordmark and G Kristjansdottir: These authors contributed equally to this work.

Authors and Affiliations

  1. Section of Rheumatology, Uppsala University, Uppsala, Sweden

    G Nordmark, M-L Eloranta & L Rönnblom

  2. Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden

    G Kristjansdottir, C Wang & A-C Syvänen

  3. Department of Rheumatology, University Hospital, Malmö, Sweden

    E Theander

  4. Department of Rheumatology, University Hospital, Linköping, Sweden

    P Eriksson

  5. Department of Rheumatology, Haukeland University Hospital, Bergen, Norway

    J G Brun & R Jonsson

  6. Section for Rheumatology, Institute of Medicine, University of Bergen, Bergen, Norway

    J G Brun

  7. Department of Medicine, Rheumatology Unit, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden

    L Padyukov

  8. Institute of Laboratory Medicine Section of MIG, Lund University, Lund, Sweden

    L Truedsson

  9. Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden

    G Alm

  10. Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway

    R Jonsson

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Correspondence to G Nordmark.

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

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Nordmark, G., Kristjansdottir, G., Theander, E. et al. Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjögren's syndrome. Genes Immun 10, 68–76 (2009). https://doi.org/10.1038/gene.2008.94

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