Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Association of C8orf13-BLK and TNFSF4 Gene Variants with Primary Sjgrens Syndrome

Nordmark1,  Gunnel, Kristjansdottir2,  Gudlaug, Appel3,  Silke, Vasaitis1,  Lilian, Kvarnstrom4,  Marika, Eriksson5,  Per, Theander6,  Elke

Rheumatology clinic, Uppsala, Sweden
Molecular Medicine, Uppsala, Sweden
Broegelmann research laboratory, Bergen, Norway
Rheumatology unit, Karolinska Institutet, Stockholm, Sweden
Rheumatology clinic, Linköping, Sweden
Rheumatology clinic, Malmö, Sweden
Cell biology, Linköping, Sweden
Clinical Immunology unit, Stavanger, Norway
Biomedical Sciences, Swedish University of Agricultural sciences, Uppsala, Sweden


Genetic factors are thought to contribute to the etiology of primary Sjögren's syndrome (pSS). The aim of this investigation was to perform a large scale candidate gene association study in patients with pSS from Sweden and Norway, to identify single nucleotide polymorphisms (SNPs) in genes with a putative role in the immune pathogenesis of pSS and in genes that have shown an association with SLE in genome wide association studies (GWA).


Genotyping was performed with the GoldenGate assay from Illumina Inc., San Diego, USA, and 1121 SNPs in 83 genes passed quality control filters and remained for association analysis. A total of 541 patients, 345 Swedish and 196 Norwegian, and 531 controls, 318 Swedish and 213 Norwegian, had a genotype success rate of >90% and were analyzed. All patients fulfilled the AECC criteria and all were Caucasians. Allele counts and genotype frequencies were compared between patients and controls by Fisher's exact test and combined p-values and OR for the Swedish and Norwegian cohorts were calculated with Cochran-Mantel-Haenzel Chi square test.


We found an association between pSS and SNPs in the C8orf13-BLK gene region and the TNFSF4 gene with a p-value of < 0.001 in the combined Swedish and Norwegian cohorts. The SNP rs12549796 in C8orf13-BLK showed an association with p = 5.8 × 10-4 and OR 1.36 (95% CI 1.15–1.63) and the SNP rs1234315 in TNFSF4 was associated with p = 7.2 × 10-4 and OR 1.35 (1.14–1.59). In addition we found an expected association between the TNPO3 gene SNP rs13246321, p = 1.2 × 10-5, OR 1.67 (1.33–2.10) which is in perfect LD with the IRF5 3'sNP rs10488631 and confirms our previous results. We found no association of these SNPs in C8orf13-BLK, TNFSF4 or TNPO3 with autoantibody status. There was no association with the BANK1, ITGAM-ITGAX, KIAA1542 or PXK genes that have shown an association with SLE in GWA studies.


We identified new candidate genes for pSS. Since BLK (B lymphoid tyrosine kinase) is only expressed in B-cells and activates nuclear transcription factors upon B cell receptor signaling and TNFSF4 (Tumor necrosis factor superfamily 4) = Ox40L, is expressed on antigen presenting cells including B cells and plasmacytoid dendritic cells, we conclude that genes involved in B cell activation are important in the pathogenesis of primary SS.

To cite this abstract, please use the following information:
Nordmark, Gunnel, Kristjansdottir, Gudlaug, Appel, Silke, Vasaitis, Lilian, Kvarnstrom, Marika, Eriksson, Per, et al; Association of C8orf13-BLK and TNFSF4 Gene Variants with Primary Sjgrens Syndrome [abstract]. Arthritis Rheum 2009;60 Suppl 10 :482
DOI: 10.1002/art.25564

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