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

Snaevar Sigurdsson, Gunnel Nordmark, Harald H.H. Göring, Katarina Lindroos, Ann Christin Wiman, Gunnar Sturfeit, Andreas Jönsen, Solbritt Rantapää-Dahlqvist, Bozena Möller, Juha Kere, Sari Koskenmies, Elisabeth Widén, Maija Leena Eloranta, Heikki Julkunen, Helga Kristjansdottir, Kristjan Steinsson, Gunnar Alm, Lars Rönnblom, Ann Christine Syvänen

Research output: Contribution to journalArticle

450 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)528-537
Number of pages10
JournalAmerican Journal of Human Genetics
Volume76
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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