Journal
JOURNAL OF RHEUMATOLOGY
Volume 36, Issue 8, Pages 1631-1638Publisher
J RHEUMATOL PUBL CO
DOI: 10.3899/jrheum.081160
Keywords
SYSTEMIC LUPUS ERYTHEMATOSUS; GENETIC ASSOCIATION; IRF5; GENETIC INTERACTION; DISEASE SUSCEPTIBILITY; TYK2
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Funding
- Finska Lakaresallskapet
- Academy of Finland
- Sigrid Juselius Foundation and Helsinki University Central Hospital Research Fund [TYH 2008248]
- Helsinki University Research Foundation
- Biomedicum Helsinki Foundation
- Finnish Union of Experts in Science (TMJ)
- Medical Research Fund of Tampere University Hospital (TH)
- Swedish Research Council (US-K)
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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 Penes 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. (First Release July 1 2009; J Rheumatol 2009;36:1631-8 doi: 10.3899/jrheum.081160)
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