RT Journal Article
SR Electronic
T1 Evidence for Genetic Association and Interaction Between the <em>TYK2</em> and <em>IRF5</em> Genes in Systemic Lupus Erythematosus
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.081160
DO 10.3899/jrheum.081160
A1 Anna Hellquist
A1 Tiina M. Järvinen
A1 Sari Koskenmies
A1 Marco Zucchelli
A1 Christina Orsmark-Pietras
A1 Linda Berglind
A1 Jaana Panelius
A1 Taina Hasan
A1 Heikki Julkunen
A1 Mauro D’Amato
A1 Ulpu Saarialho-Kere
A1 Juha Kere
YR 2009
UL http://www.jrheum.org/content/early/2009/06/27/jrheum.081160.abstract
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.