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- Hellquist, A, et al.
(författare)
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Evidence for genetic association and interaction between the TYK2 and IRF5 genes in systemic lupus erythematosus
- 2009
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 36:8, s. 1631-1638
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Järvinen, Tiina M., et al.
(författare)
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Polymorphisms of the ITGAM Gene Confer Higher Risk of Discoid Cutaneous Than of Systemic Lupus Erythematosus
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:11, s. e14212-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lupus erythematosus (LE) is a heterogeneous disease ranging from mainly skin-restricted manifestations (discoid LE [DLE] and subacute cutaneous LE) to a progressive multisystem disease (systemic LE [SLE]). Genetic association studies have recently identified several strong susceptibility genes for SLE, including integrin alpha M (ITGAM), also known as CD11b, whereas the genetic background of DLE is less clear. Principal Findings: To specifically investigate whether ITGAM is a susceptibility gene not only for SLE, but also for cutaneous DLE, we genotyped 177 patients with DLE, 85 patients with sporadic SLE, 190 index cases from SLE families and 395 population control individuals from Finland for nine genetic markers at the ITGAM locus. SLE patients were further subdivided by the presence or absence of discoid rash and renal involvement. In addition, 235 Finnish and Swedish patients positive for Ro/SSA-autoantibodies were included in a subphenotype analysis. Analysis of the ITGAM coding variant rs1143679 showed highly significant association to DLE in patients without signs of systemic disease (P-value = 4.73x10(-11), OR = 3.20, 95% CI = 2.23-4.57). Significant association was also detected to SLE patients (P-value = 8.29x10(-6), OR = 2.14, 95% CI = 1.52-3.00), and even stronger association was found when stratifying SLE patients by presence of discoid rash (P-value = 3.59x10(-8), OR = 3.76, 95% CI = 2.29-6.18). Significance: We propose ITGAM as a novel susceptibility gene for cutaneous DLE. The risk effect is independent of systemic involvement and has an even stronger genetic influence on the risk of DLE than of SLE.
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