Interferon regulatory factor 5 gene polymorphism confers risk to several rheumatic diseases and correlates with expression of alternative thymic transcripts.

Autor:	Nordang GB; Department of Medical Genetics, Oslo University Hospital, Ullevål, Kirkeveien 166, N-0407 Oslo, Norway. g.b.namlos@medisin.uio.no, Viken MK, Amundsen SS, Sanchez ES, Flatø B, Førre OT, Martin J, Kvien TK, Lie BA
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2012 Apr; Vol. 51 (4), pp. 619-26. Date of Electronic Publication: 2011 Dec 16.
DOI:	10.1093/rheumatology/ker364
Abstrakt:	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.
Databáze:	MEDLINE
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