Association of Genes in the NF-κB Pathway with Antibody-Positive Primary Sjögren's Syndrome
2013 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 78, no 5, 447-454 p.Article in journal (Refereed) Published
Primary Sjogrens syndrome (SS) is a systemic autoimmune inflammatory disease characterized by focal lymphocytic infiltrates in the lachrymal and salivary glands and autoantibodies against the SSA/Ro and SSB/La antigens. Experimental studies have shown an activation of NF-B in primary SS. NF-B activation results in inflammation and autoimmunity and is regulated by inhibitory and activating proteins. Genetic studies have shown an association between multiple autoimmune diseases and TNFAIP3 (A20) and TNIP1 (ABIN1), both repressors of NF-B and of IKBKE (IKK epsilon), which is an NF-B activator. The aim of this study was to analyse single nucleotide polymorphisms (SNPs) in the IKBKE, NFKB1, TNIP1 and TNFAIP3 genes for association with primary SS. A total of 12 SNPs were genotyped in 1105 patients from Scandinavia (Sweden and Norway, n=684) and the UK (n=421) and 4460 controls (Scandinavia, n=1662, UK, n=2798). When patients were stratified for the presence of anti-SSA and/or anti-SSB antibodies (n=868), case-control meta-analysis found an association between antibody-positive primary SS and two SNPs in TNIP1 (P=3.4x10(-5), OR=1.33, 95%CI: 1.16-1.52 for rs3792783 and P=1.3x10(-3), OR=1.21, 95%CI: 1.08-1.36 for rs7708392). A TNIP1 risk haplotype was associated with antibody-positive primary SS (P=5.7x10(-3), OR=1.47, 95%CI: 1.12-1.92). There were no significant associations with IKBKE, NFKB1 or TNFAIP3 in the meta-analysis of the Scandinavian and UK cohorts. We conclude that polymorphisms in TNIP1 are associated with antibody-positive primary SS.
Place, publisher, year, edition, pages
Wiley-Blackwell, 2013. Vol. 78, no 5, 447-454 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-101382DOI: 10.1111/sji.12101ISI: 000326077600007PubMedID: 23944604OAI: oai:DiVA.org:liu-101382DiVA: diva2:666383
Funding Agencies|Knut and Alice Wallenberg Foundation||Swedish Research Council for Medicine and Health||Swedish Rheumatism Association||King Gustaf V 80-year Foundation||County Council of ostergotland and Linkoping University Hospital||Health and Medical Care Executive Board of the Vastra Gotaland||Medical Society of Goteborg and the Region Vastra Gotaland||Strategic Research Program at Helse Bergen||Western Norway Regional Health Authority||Broegelmann Foundation||Medical Research Council UK||2013-11-222013-11-212014-03-11Bibliographically approved