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dc.creatorLi, He 
dc.creatorReksten, Tove Ragna 
dc.creatorIce, John A. 
dc.creatorKelly, Jennifer A. 
dc.creatorAdrianto, Indra 
dc.creatorRasmussen, Astrid 
dc.creatorWang, Shaofeng 
dc.creatorHe, Bo 
dc.creatorGrundahl, Kiely M. 
dc.creatorGlenn, Stuart B. 
dc.creatorMiceli-Richard, Corinne 
dc.creatorBowman, Simon 
dc.creatorLester, Sue 
dc.creatorEriksson, Per 
dc.creatorEloranta, Maija-Leena 
dc.creatorBrun, Johan G. 
dc.creatorGøransson, Lasse G. 
dc.creatorHarboe, Erna 
dc.creatorGuthridge, Joel M. 
dc.creatorKaufman, Kenneth M. 
dc.creatorKvarnström, Marika 
dc.creatorCunninghame Graham, Deborah S. 
dc.creatorPatel, Ketan 
dc.creatorAdler, Adam J. 
dc.creatorFarris, A. Darise 
dc.creatorBrennan, Michael T. 
dc.creatorChodosh, James 
dc.creatorGopalakrishnan, Rajaram 
dc.creatorWeisman, Michael H. 
dc.creatorVenuturupalli, Swamy 
dc.creatorWallace, Daniel J. 
dc.creatorHefner, Kimberly S. 
dc.creatorHouston, Glen D. 
dc.creatorHuang, Andrew J. W. 
dc.creatorHughes, Pamela J. 
dc.creatorLewis, David M. 
dc.creatorRadfar, Lida 
dc.creatorVista, Evan S. 
dc.creatorContessa E., Edgar 
dc.creatorRohrer, Michael D. 
dc.creatorStone, Donald U. 
dc.creatorVyse, Timothy J. 
dc.creatorHarley, John B. 
dc.creatorGaffney, Patrick M. 
dc.creatorJames, Judith A. 
dc.creatorTurner, Sean 
dc.creatorAlevizos, Ilias 
dc.creatorAnaya, Juan-Manuel 
dc.creatorRhodus, Nelson L. 
dc.creatorSegal, Barbara M. 
dc.creatorMontgomery, Courtney G. 
dc.creatorScofield, R. Hal 
dc.creatorKovats, Susan 
dc.creatorMariette, Xavier 
dc.creatorRönnblom, Lars 
dc.creatorWitte, Torsten 
dc.creatorRischmueller, Maureen 
dc.creatorWahren-Herlenius, Marie 
dc.creatorOmdal, Roald 
dc.creatorJonsson, Roland 
dc.creatorNg, Wan-Fai 
dc.creatorNordmark, Gunnel 
dc.creatorLessard, Christopher J. 
dc.creatorSivils, Kathy L. 
dc.date.accessioned2018-12-13T17:08:55Z
dc.date.available2018-12-13T17:08:55Z
dc.date.created2017
dc.date.issued2017
dc.identifier.issnISSN 1553-7390
dc.identifier.urihttp://repository.urosario.edu.co/handle/10336/18812
dc.description.abstractSjögren’s syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL= 6.05 × 10−14). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta= 2.59 × 10−9; odds ratio = 0.75; 95% confidence interval = 0.66–0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease. © 2017 Public Library of Science. All Rights Reserved.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.relation.ispartofPLoS Genetics, ISSN: 1553-7390, Vol. 13/No. 6 (2017)
dc.relation.urihttps://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006820&type=printable
dc.rights.urihttps://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006820
dc.titleIdentification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons
dc.typearticle
dc.subject.keywordArticle
dc.subject.keywordFemale
dc.subject.keywordFemale
dc.subject.keywordHumans
dc.subject.keywordUn-explained visual loss
dc.subject.keywordSilicone oil
dc.subject.keywordVitrectomy
dc.subject.keywordRetinal detachment
dc.subject.keywordMüller cells
dc.subject.keywordNeuronal apoptosis
dc.subject.keywordPotassium
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.type.spaArtículo
dc.rights.accesoAbierto (Texto Completo)
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.source.bibliographicCitationHelmick, C.G., Felson, D.T., Lawrence, R.C., Gabriel, S., Hirsch, R., Kwoh, C.K., Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I (2008) Arthritis Rheum, 58 (1), pp. 15-25. , 18163481
dc.rights.cchttps://creativecommons.org/publicdomain/zero/1.0/
dc.creator.googleLi, He
dc.creator.googleReksten, Tove Ragna
dc.creator.googleIce, John A.
dc.creator.googleKelly, Jennifer A.
dc.creator.googleAdrianto, Indra
dc.creator.googleRasmussen, Astrid
dc.creator.googleWang, Shaofeng
dc.creator.googleHe, Bo
dc.creator.googleGrundahl, Kiely M.
dc.creator.googleGlenn, Stuart B.
dc.creator.googleMiceli-Richard, Corinne
dc.creator.googleBowman, Simon
dc.creator.googleLester, Sue
dc.creator.googleEriksson, Per
dc.creator.googleEloranta, Maija-Leena
dc.creator.googleBrun, Johan G.
dc.creator.googleGøransson, Lasse G.
dc.creator.googleHarboe, Erna
dc.creator.googleKaufman, Kenneth M.
dc.creator.googleKvarnström, Marika
dc.creator.googleCunninghame Graham, Deborah S.
dc.creator.googlePatel, Ketan
dc.creator.googleAdler, Adam J.
dc.creator.googleFarris, A. Darise
dc.creator.googleBrennan, Michael T.
dc.creator.googleChodosh, James
dc.creator.googleGopalakrishnan, Rajaram
dc.creator.googleWeisman, Michael H.
dc.creator.googleVenuturupalli, Swamy
dc.creator.googleWallace, Daniel J.
dc.creator.googleHefner, Kimberly S.
dc.creator.googleHouston, Glen D.
dc.creator.googleHuang, Andrew J. W.
dc.creator.googleHughes, Pamela J.
dc.creator.googleLewis, David M.
dc.creator.googleRadfar, Lida
dc.creator.googleVista, Evan S.
dc.creator.googleContessa E., Edgar
dc.creator.googleRohrer, Michael D.
dc.creator.googleStone, Donald U.
dc.creator.googleVyse, Timothy J.
dc.creator.googleHarley, John B.
dc.creator.googleGaffney, Patrick M.
dc.creator.googleJames, Judith A.
dc.creator.googleTurner, Sean
dc.creator.googleAlevizos, Ilias
dc.creator.googleAnaya, Juan-Manuel
dc.creator.googleRhodus, Nelson L.
dc.creator.googleSegal, Barbara M.
dc.creator.googleMontgomery, Courtney G.
dc.creator.googleScofield, R. Hal
dc.creator.googleKovats, Susan
dc.creator.googleMariette, Xavier
dc.creator.googleMariette, Xavier
dc.creator.googleRönnblom, Lars
dc.creator.googleWitte, Torsten
dc.creator.googleRischmueller, Maureen
dc.creator.googleWahren-Herlenius, Marie
dc.creator.googleOmdal, Roald
dc.creator.googleJonsson, Roland
dc.creator.googleNg, Wan-Fai
dc.creator.googleNordmark, Gunnel
dc.creator.googleLessard, Christopher J.
dc.creator.googleSivils, Kathy L.
dc.identifier.doihttps://doi.org/10.1371/journal.pgen.1006820
dc.relation.citationIssueNo. 6
dc.relation.citationTitlePLoS Genetics
dc.relation.citationVolumeVol. 13


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