PT  - JOURNAL ARTICLE
AU  - Anna Hellquist
AU  - Tiina M. Järvinen
AU  - Sari Koskenmies
AU  - Marco Zucchelli
AU  - Christina Orsmark-Pietras
AU  - Linda Berglind
AU  - Jaana Panelius
AU  - Taina Hasan
AU  - Heikki Julkunen
AU  - Mauro D’Amato
AU  - Ulpu Saarialho-Kere
AU  - Juha Kere
TI  - Evidence for Genetic Association and Interaction Between the <em>TYK2</em> and <em>IRF5</em> Genes in Systemic Lupus Erythematosus
AID  - 10.3899/jrheum.081160
DP  - 2009 Jun 30
TA  - The Journal of Rheumatology
PG  - jrheum.081160
4099  - http://www.jrheum.org/content/early/2009/06/27/jrheum.081160.short
4100  - http://www.jrheum.org/content/early/2009/06/27/jrheum.081160.full
AB  - 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.