Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus

2.50
Hdl Handle:
http://hdl.handle.net/2336/67758
Title:
Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus
Authors:
Sigurdsson, Snaevar; Nordmark, Gunnel; Göring, Harald H H; Lindroos, Katarina; Wiman, Ann-Christin; Sturfelt, Gunnar; Jönsen, Andreas; Rantapää-Dahlqvist, Solbritt; Möller, Bozena; Kere, Juha; Koskenmies, Sari; Widén, Elisabeth; Eloranta, Maija-Leena; Julkunen, Heikki; Kristjansdottir, Helga; Steinsson, Kristjan; Alm, Gunnar; Rönnblom, Lars; Syvänen, Ann-Christine
Citation:
Am. J. Hum. Genet. 2005, 76(3):528-37
Issue Date:
1-Mar-2005
Abstract:
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms (SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control individuals for joint linkage and association with SLE. In two of the genes--the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes--we identified SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P<10(-7)) with SLE. TYK2 binds to the type I IFN receptor complex and IRF5 is a regulator of type I IFN gene expression. Thus, our results support a disease mechanism in SLE that involves key components of the type I IFN system.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1196404

Full metadata record

DC FieldValue Language
dc.contributor.authorSigurdsson, Snaevar-
dc.contributor.authorNordmark, Gunnel-
dc.contributor.authorGöring, Harald H H-
dc.contributor.authorLindroos, Katarina-
dc.contributor.authorWiman, Ann-Christin-
dc.contributor.authorSturfelt, Gunnar-
dc.contributor.authorJönsen, Andreas-
dc.contributor.authorRantapää-Dahlqvist, Solbritt-
dc.contributor.authorMöller, Bozena-
dc.contributor.authorKere, Juha-
dc.contributor.authorKoskenmies, Sari-
dc.contributor.authorWidén, Elisabeth-
dc.contributor.authorEloranta, Maija-Leena-
dc.contributor.authorJulkunen, Heikki-
dc.contributor.authorKristjansdottir, Helga-
dc.contributor.authorSteinsson, Kristjan-
dc.contributor.authorAlm, Gunnar-
dc.contributor.authorRönnblom, Lars-
dc.contributor.authorSyvänen, Ann-Christine-
dc.date.accessioned2009-05-11T09:46:41Z-
dc.date.available2009-05-11T09:46:41Z-
dc.date.issued2005-03-01-
dc.date.submitted2009-05-11-
dc.identifier.citationAm. J. Hum. Genet. 2005, 76(3):528-37en
dc.identifier.issn0002-9297-
dc.identifier.pmid15657875-
dc.identifier.doi10.1086/428480-
dc.identifier.urihttp://hdl.handle.net/2336/67758-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractSystemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms (SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control individuals for joint linkage and association with SLE. In two of the genes--the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes--we identified SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P<10(-7)) with SLE. TYK2 binds to the type I IFN receptor complex and IRF5 is a regulator of type I IFN gene expression. Thus, our results support a disease mechanism in SLE that involves key components of the type I IFN system.en
dc.language.isoenen
dc.publisherUniversity of Chicago Pressen
dc.relation.urlhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1196404en
dc.subject.meshAllelesen
dc.subject.meshCase-Control Studiesen
dc.subject.meshDNA-Binding Proteinsen
dc.subject.meshFemaleen
dc.subject.meshFinlanden
dc.subject.meshGene Frequencyen
dc.subject.meshHumansen
dc.subject.meshIcelanden
dc.subject.meshInterferon Regulatory Factorsen
dc.subject.meshLinkage (Genetics)en
dc.subject.meshLupus Erythematosus, Systemicen
dc.subject.meshMaleen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshProtein-Tyrosine Kinasesen
dc.subject.meshSwedenen
dc.subject.meshTYK2 Kinaseen
dc.subject.meshTranscription Factorsen
dc.titlePolymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosusen
dc.typeArticleen
dc.contributor.departmentMolecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.en
dc.identifier.journalAmerican journal of human geneticsen

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