Evidence for genetic association and interaction between the TYK2 and IRF5 genes in systemic lupus erythematosus

Anna Hellquist, Tiina M. Järvinen, Sari Koskenmies, Marco Zucchelli, Christina Orsmark-Pietras, Linda Berglind, Jaana Panelius, Taina Hasan, Heikki Julkunen, Mauro D'Amato, Ulpu Saarialho-Kere, Juha Kere

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Objective. Several candidate genes have been implicated in susceptibility for systemic lupus erythematosus (SLE), a complex autoimmune disease. The proposed genes include members of the type I interferon (IFN) pathway and genes involved in immunological defense functions. Our aim was to systematically replicate 6 such genes, TYK2, IRF5, CTLA4, PDCD1, FCGR2A, and NOD2. Methods. Single-nucleotide polymorphisms in TYK2, IRF5, CTLA4, PDCD1, FCGR2A, and NOD2 were genotyped in 277 SLE patients and 356 healthy controls from Finland, giving a power of 42%-70% for different genes at published allele frequencies. Results. Significant association was seen for rs2304256 (p = 0.0001) and rs12720270 (p = 0.0031) in TYK2 and rs10954213 (p = 0.0043) in IRF5 in our samples, but not for the other genes. We found evidence for genetic interaction (p = 0.014) between rs2304256 in TYK2 and rs10954213 in IRF5, both members of the type I IFN pathway, strengthening the role of the type I IFN pathway in the pathogenesis of SLE. Conclusion. The IFN pathway genes IRF5 and TYK2 may act epistatically in increasing risk for SLE, but our lack of replication does not exclude effects of the other genes studied. The Journal of Rheumatology

Original languageEnglish
Pages (from-to)1631-1638
Number of pages8
JournalThe Journal of Rheumatology
Issue number8
Publication statusPublished - 1 Aug 2009
Externally publishedYes


  • Disease susceptibility
  • Genetic association
  • Genetic interaction
  • IRF5
  • Systemic lupus erythematosus
  • TYK2

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