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Association of STAT4 Polymorphism with Severe Renal Insufficiency in Lupus Nephritis
Uppsala University, Sweden .
Uppsala University, Sweden Uppsala University, Sweden .
Karolinska University Hospital, Sweden Karolinska Institute, Sweden .
Lund University, Sweden .
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2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 12, 84450- p.Article in journal (Refereed) Published
Abstract [en]

Lupus nephritis is a cause of significant morbidity in systemic lupus erythematosus (SLE) and its genetic background has not been completely clarified. The aim of this investigation was to analyze single nucleotide polymorphisms (SNPs) for association with lupus nephritis, its severe form proliferative nephritis and renal outcome, in two Swedish cohorts. Cohort I (n = 567 SLE cases, n = 512 controls) was previously genotyped for 5676 SNPs and cohort II (n = 145 SLE cases, n = 619 controls) was genotyped for SNPs in STAT4, IRF5, TNIP1 and BLK. Case-control and case-only association analyses for patients with lupus nephritis, proliferative nephritis and severe renal insufficiency were performed. In the case-control analysis of cohort I, four highly linked SNPs in STAT4 were associated with lupus nephritis with genome wide significance with p = 3.7x10(-9), OR 2.20 for the best SNP rs11889341. Strong signals of association between IRF5 and an HLA-DR3 SNP marker were also detected in the lupus nephritis case versus healthy control analysis (pless than0.0001). An additional six genes showed an association with lupus nephritis with pless than0.001 (PMS2, TNIP1, CARD11, ITGAM, BLK and IRAK1). In the case-only meta-analysis of the two cohorts, the STAT4 SNP rs7582694 was associated with severe renal insufficiency with p = 1.6x10(-3) and OR 2.22. We conclude that genetic variations in STAT4 predispose to lupus nephritis and a worse outcome with severe renal insufficiency.

Place, publisher, year, edition, pages
Public Library of Science , 2013. Vol. 8, no 12, 84450- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-103872DOI: 10.1371/journal.pone.0084450ISI: 000329117900096OAI: diva2:692529
Available from: 2014-01-31 Created: 2014-01-30 Last updated: 2014-02-06

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Sjöwall, Christoffer
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Division of Inflammation MedicineFaculty of Health SciencesDepartment of Rheumatology
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