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Type: Journal article
Title: Polymorphism in the 5 ' regulatory region of the B-lymphocyte activating factor gene is associated with the Ro/La autoantibody response and serum BAFF levels in primary Sjogren's syndrome
Author: Nossent, J.
Lester, S.
Zahra, D.
Mackay, C.
Rischmueller, M.
Citation: Rheumatology, 2008; 47(9):1311-1316
Publisher: Oxford Univ Press
Issue Date: 2008
ISSN: 1462-0324
Statement of
J. C. Nossent, S. Lester, D. Zahra, C. R. Mackay and M. Rischmueller
Abstract: Objective. 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.
Keywords: B-lymphocyte activating factor; Sjögren's syndrome; Polymorphism
RMID: 0020082485
DOI: 10.1093/rheumatology/ken246
Appears in Collections:Medicine publications

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