{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T15:29:58Z","timestamp":1781018998503,"version":"3.54.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T00:00:00Z","timestamp":1404950400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T00:00:00Z","timestamp":1404950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease risk. Interferon regulatory factor 5 (IRF5) is a regulator of type I interferon induction. Recently, researchers have described an association between multiple single-nucleotide polymorphisms of the <jats:italic>IRF5<\/jats:italic> gene and some rheumatic disorders. In this study, we aimed to evaluate whether three different haplotype blocks within the <jats:italic>IRF5<\/jats:italic> locus which have been shown to alter the protein function are involved in the risk of CV events occurring in Spanish RA patients.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Three <jats:italic>IRF5<\/jats:italic> polymorphisms (rs2004640, rs2070197 and rs10954213) representative of each haplotype group were genotyped by performing TaqMan assays using a 7900HT Fast Real-Time PCR System with tissue from a total of 2,137 Spanish patients diagnosed with RA. Among them, 390 (18.2%) had experienced CV events. The relationship of <jats:italic>IRF5<\/jats:italic> genotypes and haplotypes to CV events was tested using Cox regression.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Male sex, age at RA diagnosis and most traditional risk factors (hypertension, dyslipidemia and smoking habit) were associated with increased risk for CV events in the RA population. Interestingly, a protective effect of both <jats:italic>IRF5<\/jats:italic> rs2004640 GG and <jats:italic>IRF5<\/jats:italic> rs10954213 GG genotypes against the risk for CV events after adjusting the results for sex, age at RA diagnosis and traditional CV disease risk factors was observed (hazard ratio (HR)\u2009=\u20090.6, 95% confidence interval (CI)\u2009=\u20090.38 to 0.92, <jats:italic>P<\/jats:italic>\u2009=\u20090.02; and HR\u2009=\u20090.58, 95% CI\u2009=\u20090.36 to 0.95, <jats:italic>P<\/jats:italic>\u2009=\u20090.03, respectively). Moreover, we detected a protective effect of the GTG haplotype against the risk for CV events after adjusting the results for potential confounding factors (HR\u2009=\u20090.72, 95% CI\u2009=\u20090.56 to 0.93, <jats:italic>P<\/jats:italic>\u2009=\u20090.012).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Our results reveal that <jats:italic>IRF5<\/jats:italic> gene variants are associated with risk of CV events in patients with RA.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar4608","type":"journal-article","created":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T09:02:09Z","timestamp":1404982929000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Interferon regulatory factor 5 genetic variants are associated with cardiovascular disease in patients with rheumatoid arthritis"],"prefix":"10.1186","volume":"16","author":[{"given":"Mercedes","family":"Garc\u00eda-Berm\u00fadez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"L\u00f3pez-Mej\u00edas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Genre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santos","family":"Casta\u00f1eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Llorca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Gonz\u00e1lez-Juanatey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Corrales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Ubilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A","family":"Miranda-Filloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinitario","family":"Pina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"G\u00f3mez-Vaquero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Rodr\u00edguez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjam\u00edn","family":"Fern\u00e1ndez-Guti\u00e9rrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Balsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Pascual-Salcedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J","family":"L\u00f3pez-Longo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Carreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A","family":"Gonz\u00e1lez-Gay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,7,10]]},"reference":[{"key":"4373_CR1","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1136\/annrheumdis-2011-200726","volume":"71","author":"JA Avina-Zubieta","year":"2012","unstructured":"Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D: Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. 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