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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

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 T-->C, -2704 T-->C, -2701 T-->A, -871 C-->T), 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.

Type Journal
ISBN 1462-0332 (Electronic)
Authors Nossent, J. C. Lester, S. Zahra, D. Mackay, C. R. Rischmueller, M.
Publisher Name RHEUMATOLOGY
Published Date 2008-09-01 00:00:00
Published Volume 47
Published Issue 9
Published Pages 1311-6
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18617551
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?10142_10254/08 Nossent Rheumatology 1311.pdf