Nossent, J.Lester, S.Zahra, D.Mackay, C.Rischmueller, M.2009-11-302009-11-302008Rheumatology, 2008; 47(9):1311-13161462-03241462-0332http://hdl.handle.net/2440/54107Objective. To investigate the association between haplotypes in the 5' regulatory region of the B-lymphocyte activating factor (BAFF) gene, disease susceptibility and serum BAFF (s-BAFF) levels in Caucasian primary SS (pSS) patients. Methods. Case–control study in an established pSS cohort with PCR–RFLP genotyping for four SNPs (-2841 TC, -2704 TC, -2701 TA, -871 CT), which tag a haplotype block in the 5' regulatory region of the BAFF gene and s-BAFF determination by ELISA. Results. s-BAFF levels were elevated in Ro/La-positive pSS patients (n = 85, 1770 pg/ml) compared with both Ro/La-negative pSS patients (n = 27, 1193 pg/ml) and controls (n = 59, 1171 pg/ml), P < 0.001. s-BAFF increased with diversification of the anti-Ro/La antibody response, but was not correlated with age, RF or immunoglobulin G levels. There were four common BAFF haplotypes. While the CTAT haplotype was associated with Ro/La-positive pSS [odds ratio (OR) 2.6; 95% CI 1.7, 4.1; P = 0.00004], the TTTT haplotype was associated with elevated s-BAFF in autoantibody-positive pSS (n = 85; 88% females; P = 0.008). The shared -871 T allele had no independent contribution to disease susceptibility or s-BAFF. Conclusions. Disease susceptibility for Ro/La-positive pSS is increased with the CTAT haplotype, but not associated with high s-BAFF levels. Elevated s-BAFF levels in pSS are associated with the TTTT haplotype and may be a secondary phenomenon in Ro/La-positive pSS. While both haplotypes carry the -871 T allele, this allele is not independently associated with disease susceptibility.enB-lymphocyte activating factorSjögren's syndromePolymorphismJournal article002008248510.1093/rheumatology/ken2460002589606000092-s2.0-5084908610242120Lester, S. [0000-0003-3013-2701]Rischmueller, M. [0000-0001-5057-3286]