Interferon regulatory factor 5 gene polymorphism confers risk to several rheumatic diseases and correlates with expression of alternative thymic transcripts.
Objectives. Polymorphisms in genes related to the IFN pathway were investigated for susceptibility to rheumatic diseases and correlation with gene expression in thymus.Methods. Forty-five polymorphisms were genotyped in Norwegian patients with RA (n = 518), JIA (n = 440), SLE (n = 154) and healthy c...
| Publicado en: | Rheumatology Vol. 51; no. 4; pp. 619 - 627 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Apr2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=73765072&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 73765072 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14620324 DN9 jtl: Rheumatology issn: 14620324 maglogo: N pubinfo: dt: Apr2012 vid: 51 iid: 4 pid: 622 pub: Oxford University Press / USA artinfo: ui: 73765072 104538882 104538882 10.1093/rheumatology/ker364 73765072 ppf: 619 ppct: 8 formats: tig: atl: Interferon regulatory factor 5 gene polymorphism confers risk to several rheumatic diseases and correlates with expression of alternative thymic transcripts. aug: au: Nordang, Gry B. N. Viken, Marte K. Amundsen, Silja S. Sanchez, Elena S. Flatø, Berit Førre, Øystein T. Martin, Javier Kvien, Tore K. Lie, Benedicte A. affil: Department of Immunology, Department of Medical Genetics, Ullevål, Centre for Immune Regulation, Department of Immunology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway, Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada, Spain, Department of Rheumatology, Oslo University Hospital, Rikshospitalet and Faculty of Medicine, University of Oslo and Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. sug: subj: Polymorphism, Genetic Autoimmune Diseases Risk Factors Thymus Gland Physiology Human Genomics Arthritis, Rheumatoid Lupus Erythematosus, Systemic Arthritis, Juvenile Rheumatoid Gene Expression Interferons Norway Case Control Studies Spain Odds Ratio Confidence Intervals ab: Objectives. Polymorphisms in genes related to the IFN pathway were investigated for susceptibility to rheumatic diseases and correlation with gene expression in thymus.Methods. Forty-five polymorphisms were genotyped in Norwegian patients with RA (n = 518), JIA (n = 440), SLE (n = 154) and healthy controls (n = 756). Forty-two thymic samples were used for gene expression analysis. Six hundred and fifty SLE patients and 737 healthy controls from Spain were available for replication.Results. We found a novel association between interferon regulatory factor 5 (IRF5), rs2004640 and JIA, in particular with the polyarthritis RF-negative patients [odds ratio (OR) = 1.60; 95% confidence interval (CI) 1.17, 2.20; P = 0.003]. Also, we confirmed the associations between rs2004640 and SLE (OR = 1.95; 95% CI 1.50, 2.53; P = 3.75 × 10−7), which was further strengthened in a meta-analysis (OR = 1.44; 95% CI 1.36, 1.52; P = 2.11 × 10−37). Suggestive evidence of association between rs2004640 and RA was found in the Norwegian discovery cohort (OR = 1.19; 95% CI 1.02, 1.40; P = 0.029) and strengthened in a meta-analysis (OR = 1.11; 95% CI 1.05, 1.18; P = 0.00028). Expression levels of exon 1B IRF5 transcripts were dependent on the presence of the rs2004640*T risk allele in thymic tissue, while exon 1A transcript levels correlated with IRF5 promoter CGGGG-indel variants.Conclusion. The IFN pathway gene, IRF5, is a common susceptibility factor for several rheumatic and autoimmune diseases, and risk variants are correlated with expression of alternative IRF5 transcripts in thymus implying a regulatory role. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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