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

• Published in: The American Journal of Human Genetics
• Main 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
• Other Authors: Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
• Format: Article in Journal/Newspaper
• Language: English
• Published: University of Chicago Press 2009
• Subjects: Alleles; Case-Control Studies; DNA-Binding Proteins; Female; Finland; Gene Frequency; Humans; Iceland; Interferon Regulatory Factors; Linkage (Genetics); Lupus Erythematosus; Systemic; Male; Polymorphism; Single Nucleotide; Protein-Tyrosine Kinases; Sweden; TYK2 Kinase; Transcription Factors
• Online Access: http://hdl.handle.net/2336/67758; https://doi.org/10.1086/428480

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field 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.