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Variation in STAT4 is associated with systemic lupus erythematosus in a Finnish family cohort
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
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2010 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 69, no 5, 883-886 p.Article in journal (Refereed) Published
Abstract [en]


To investigate if 10 single nucleotide polymorphisms (SNPs) and haplotypes in the STAT4 gene, previously associated with SLE in a Swedish case-control cohort, also are associated with SLE risk in a Finnish SLE family cohort.


Genotyping was performed in 192 Finnish families, with 237 affected individuals and their healthy relatives, using the SNPstream genotyping system.


TDT analysis provided the strongest signal of association for two linked SNPs; rs7582694 (P-value = 0.002, OR = 2.57) and rs10181656 (P-value = 0.001, OR = 2.53). We further performed haplotype association analysis using a sliding window approach which showed that the strongest association signal originates from SNPs in intron 3 of STAT4.


Our results provide evidence that the main association signal for STAT4 with SLE previously reported in Caucasians is the same in the Finnish population. This is the first study that confirms the association of STAT4 with SLE in a family cohort.

Place, publisher, year, edition, pages
2010. Vol. 69, no 5, 883-886 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-117769DOI: 10.1136/ard.2009.112284ISI: 000276982300021PubMedID: 19717398OAI: oai:DiVA.org:uu-117769DiVA: diva2:298360

De två första författarna delar förstaförfattarskapet

Available from: 2010-02-22 Created: 2010-02-22 Last updated: 2013-03-06Bibliographically approved
In thesis
1. Genetic Analyses of Multiple Sclerosis and Systemic Lupus Erythematosus: From Single Markers to Genome-Wide Data
Open this publication in new window or tab >>Genetic Analyses of Multiple Sclerosis and Systemic Lupus Erythematosus: From Single Markers to Genome-Wide Data
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In autoimmune diseases an individual’s immune system becomes targeted at the body’s own healthy cells. The aim of this thesis was to identify genetic risk factors for the two autoimmune diseases multiple sclerosis (MS) and systemic lupus erythematosus (SLE). In Study I, we found that genetic variation in the interferon regulatory factor 5 gene (IRF5), previously shown to be associated with SLE, rheumatoid arthritis and inflammatory bowel diseases, was associated also with MS. An insertion/deletion polymorphism in the first intron of IRF5 is as a good functional candidate for this association. IRF5, together with the signal transducer and activator of transcription 4 gene (STAT4), are the most important genetic risk factors for SLE, outside the HLA region. In Study II we showed using a family-based study design that genetic variation in STAT4 is associated with SLE also in the Finnish population. In Study III, we investigated a STAT4 risk allele for SLE for its association with cardiovascular disease in SLE patients. The risk allele of STAT4 proved to be strongly associated with ischemic cerebrovascular disease and anti-phospholipid antibodies in SLE patients. A possible mechanism for this association is that the risk allele leads to increased production of pro-thrombotic anti-phospholipid antibodies, which in turn increases the risk for stroke. Both IRF5 and STAT4 are involved in signalling of the type I interferon system. In Study IV, we investigated 78 additional genes in this system for their association with SLE in a Swedish cohort. The most promising results were followed up in additional patients and controls from Sweden and the US. Two novel SLE genes were identified. In Study V a large follow-up of a genome-wide association study was performed. Five new SLE loci were identified: TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10. A number of genes previously shown to be associated with other autoimmune diseases were also tested for association with SLE. This analysis identified the type I interferon system gene IFIH1 as a novel SLE risk locus. These studies confirms the central role of the type I interferon system in SLE and further suggests common genetic risk factors in autoimmunity.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 64 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 528
Systemic lupus erythematosus, Multiple Sclerosis, Association study, Type I interferon system, Single nucleotide polymorphism
National Category
Medical Genetics
Research subject
Molecular Medicine
urn:nbn:se:uu:diva-117776 (URN)978-91-554-7736-3 (ISBN)
Public defence
2010-04-16, Enghoffsalen, University Hospital, entrance 50, ground floor, Uppsala, 13:15 (English)
Available from: 2010-03-25 Created: 2010-02-22 Last updated: 2010-03-31Bibliographically approved

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