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Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome

Genes & Immunity volume 12, pages 100–109 (2011)Cite this article

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Abstract

We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10−5, OR 1.68, the family with sequence similarity 167 member A–B-lymphoid tyrosine kinase (FAM167A–BLK) locus, P=4.7 × 10−4, OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10−4, OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.

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Acknowledgements

We thank Rezvan Kiani, Linda Öjkvist, Hawa Camara, Käth Nilsson and Raul Figueroa for collecting patient samples, the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study for providing control samples, the Malmö Diet and Cancer Study/Malmö Preventive Medicine program for storing and providing DNA and Region Skånes kompetenscentrum för klinisk forskning (RSKC), Malmö for isolating DNA. This work was supported by Knut and Alice Wallenberg Foundation (SNP Technology Platform in Uppsala); Swedish Research Council for Medicine (A-CS, LR), the Swedish Rheumatism Association (LR, EB, GN, ET); the King Gustaf V 80-year Foundation (LR, EB, GN, PS); Ulla and Roland Gustafsson Foundation (LR); Torsten and Ragnar Söderberg Foundation (LR); COMBINE (LR, MW-H); FORSS (PS) and the Strategic Research Program at Helse Bergen, Western Norway Regional Health Authority (LGG, SA, ND, JGB, MVJ, RJ); the Broegelmann Foundation (SA, ND, JGB, MVJ, RJ); the Norwegian Foundation for Health and Rehabilitation (EH); postdoctoral grants from L and R Åkerhams and S and B Engströms foundations (GN), the Agnes and Mac Rudberg foundation (GK), Anna-Greta Crafoord Foundation and from Malmö University Hospital cancer foundation (ET).

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Authors and Affiliations

  1. Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden

    G Nordmark, G Kristjansdottir, L Vasaitis, M-L Eloranta, E Baecklund & L Rönnblom

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

    G Kristjansdottir, P Lundmark, A Lundmark & A-C Syvänen

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

    E Theander

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

    S Appel, N Delaleu, M V Jonsson & R Jonsson

  5. Division of Rheumatology, Department of Clinical Experimental Medicine, Linköping University, Linköping, Sweden

    P Eriksson & C Sjöwall

  6. Department of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden

    M Kvarnström & M Wahren-Herlenius

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

    J G Brun

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

    J G Brun, M V Jonsson & R Jonsson

  9. Department of Internal Medicine, Clinical immunology unit, Stavanger University Hospital, Stavanger, Norway

    E Harboe, L G Gøransson, S J Johnsen & R Omdal

  10. Division of Cell Biology, Department of Clinical Experimental Medicine, Linköping University, Linköping, Sweden

    P Söderkvist

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

    G Alm

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Nordmark, G., Kristjansdottir, G., Theander, E. et al. Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome. Genes Immun 12, 100–109 (2011). https://doi.org/10.1038/gene.2010.44

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