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

Genes Immun. 2011 Mar;12(2):100-9. doi: 10.1038/gene.2010.44. Epub 2010 Sep 23.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interleukin-6 / genetics
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Norway
  • OX40 Ligand / genetics*
  • Polymorphism, Single Nucleotide
  • Protein-Tyrosine Kinases / genetics*
  • STAT4 Transcription Factor / genetics
  • Sjogren's Syndrome / enzymology
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / immunology*
  • Sweden
  • Trans-Activators / genetics*


  • EBF1 protein, human
  • IRF5 protein, human
  • Interferon Regulatory Factors
  • Interleukin-6
  • OX40 Ligand
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • TNFSF4 protein, human
  • Trans-Activators
  • Protein-Tyrosine Kinases