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Genetic variation in promoter sequence of B cell-activating factor gene is associated with increased risk of myositis development
  1. M Faustova,
  2. P Novota,
  3. O Krystufkova,
  4. H Hulejova,
  5. J Vencovsky
  1. Department of Molecular Biology and Immunogenetics, Institute of Rheumatology, Prague, Czech Republic

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The protein encoded by B cell-activating factor (BAFF) gene is a member of the tumour necrosis factor (ligand) superfamily. This protein is expressed by myeloid line cells (dendritic cells, macrophages, monocytes), partly by T cells and is secreted mostly by dendritic cells. It increases the survival of B cells in vitro and regulates peripheral B cells. It also seems to play a role in T cell activation providing a co-stimulatory signal. The promoter region of BAFF gene contains several known sites with single nucleotide polymorphism (SNPs). An association between some of these polymorphisms and autoimmune diseases was shown; however, some discrepant results have been obtained. In the past, the authors have identified elevated levels of BAFF protein in patients with polymyositis (PM) and dermatomyositis (DM), particularly in anti-Jo-1 positive patients.


34 patients with PM and 23 with DM have been investigated and compared with 50 healthy controls. Four SNPs located upstream in BAFF gene (−2841 T C, −2704 T C, −2701 T A, −871 C T) have been analysed by direct sequencing. The statistical significance of alleles and genotypes was calculated using the Fisher exact test or χ² test respectively. p Values were corrected for multiple testing; the strength of the association was expressed by calculating the OR with 95% CI.


The authors found a statistically significant association in two out of four investigated SNPs with myositis development. The frequency of −2841 T allele (rs9514827) was identified to be 76% in patients with PM/DM while only 58% in the control group of healthy individuals (p<0.05, OR 23 (95% CI 29 to 3.99)). Similarly, the frequency of allele −2704C (rs3759467) was higher in patients than in healthy control subjects (25% vs 7%, p<0.001, OR 43 (95% CI 86 to 10.53)). For the two remaining polymorphisms, no significant difference between patients and controls was found.


The authors have recently identified increased levels of BAFF protein in patients with PM and DM. Here they show that the disease is associated with disproportionate representation of alleles in the two SNPs of the BAFF gene. The risk is assumed to be associated with the presence of −2841 T/T genotype in SNP rs9514827 and the −2704 C/C genotype in SNP rs3759467. The association with serum BAFF and anti-Jo-1 levels is currently being analysed in order to explore the potential functional effect of SNPs on regulation of BAFF expression.

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