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Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjögren's syndrome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Reumatologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
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2009 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 10, no 1, 68-76 p.Article in journal (Refereed) Published
Abstract [en]

Primary Sjögren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) >1.4 and P-values <0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P=2.5 × 10−9. The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.

Place, publisher, year, edition, pages
2009. Vol. 10, no 1, 68-76 p.
Keyword [en]
primary Sjögren's syndrome, IRF5, STAT4, single nucleotide polymorphisms, insertion–deletion polymorphism
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:uu:diva-103500DOI: 10.1038/gene.2008.94ISI: 000262580600010PubMedID: 19092842OAI: oai:DiVA.org:uu-103500DiVA: diva2:218343
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De två första författarna delar förstaförfattarskapet

Available from: 2009-05-19 Created: 2009-05-19 Last updated: 2017-12-13Bibliographically approved

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Nordmark, GunnelWang, ChuanEloranta, Maija-LeenaRönnblom, LarsSyvänen, Ann Christine

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