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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.
Rheumatology (Oxford). 2008 Sep; 47(9):1311-6.R

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.

Authors+Show Affiliations

Department of Rheumatology, PO Box 14, University Hospital Northern Norway, N-9038 Tromsø, Norway. hans.nossent@unn.noNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18617551

Citation

Nossent, J C., et al. "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." Rheumatology (Oxford, England), vol. 47, no. 9, 2008, pp. 1311-6.
Nossent JC, Lester S, Zahra D, et al. 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. Rheumatology (Oxford). 2008;47(9):1311-6.
Nossent, J. C., Lester, S., Zahra, D., Mackay, C. R., & Rischmueller, M. (2008). 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. Rheumatology (Oxford, England), 47(9), 1311-6. https://doi.org/10.1093/rheumatology/ken246
Nossent JC, et al. 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. Rheumatology (Oxford). 2008;47(9):1311-6. PubMed PMID: 18617551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Nossent,J C, AU - Lester,S, AU - Zahra,D, AU - Mackay,C R, AU - Rischmueller,M, Y1 - 2008/07/10/ PY - 2008/7/12/pubmed PY - 2008/10/15/medline PY - 2008/7/12/entrez SP - 1311 EP - 6 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 47 IS - 9 N2 - 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. SN - 1462-0332 UR - https://www.unboundmedicine.com/medline/citation/18617551/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_ DB - PRIME DP - Unbound Medicine ER -