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dc.contributor.authorLing, Stephanie F.
dc.contributor.authorViatte, Sebastien
dc.contributor.authorLunt, Mark
dc.contributor.authorVan Sijl, Alper M
dc.contributor.authorSilva Fernández, Lucía 
dc.contributor.authorSymmons, Deborah P. M.
dc.contributor.authorYoung, Adam
dc.contributor.authorMacgregor, Alexander J
dc.contributor.authorBarton, Anne
dc.date.accessioned2017-09-15T09:39:25Z
dc.date.available2017-09-15T09:39:25Z
dc.date.issued2016-11
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pubmed/?term=27274008es
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244675/es
dc.identifier.urihttp://hdl.handle.net/20.500.11940/9562
dc.description.abstractRheumatoid arthritis (RA) susceptibility HLA-DRB1 haplotypes based on amino acid positions 11/13, 71, and 74 predict radiographic damage. The mechanism of action is unknown, but it may be mediated by inflammation. We undertook this study to systematically investigate the effect of these amino acids on nonradiographic measures of disease activity/outcomes. We tested the association of RA susceptibility HLA-DRB1 amino acids with the C-reactive protein (CRP) level, the tender joint count (TJC), the swollen joint count (SJC), the Disease Activity Score in 28 joints (DAS28), and the Health Assessment Questionnaire (HAQ) score in the Norfolk Arthritis Register (NOAR) and Early Rheumatoid Arthritis Study (ERAS) cohorts. Longitudinal modeling of disease activity/outcomes was performed using generalized linear latent and mixed models. Mediation analysis was performed using directed acyclic graphs to investigate the paths from genetic factors to outcome. A total of 2,158 patients were available for analysis in the NOAR cohort. Valine at position 11 showed the strongest association with the CRP level (P = 2.21 × 10(-6) ), the SJC (P = 7.51 × 10(-6) ), and the DAS28 (P = 0.002); it was marginally associated with the HAQ score (P = 0.044) but not with the TJC. The same amino acid and haplotype risk hierarchy observed for susceptibility and radiographic severity was observed for the CRP level and nonradiographic measures of disease activity/outcome, apart from the TJC. The results were replicated in the ERAS cohort. The effect of valine at position 11 on the SJC was mainly mediated by anti-citrullinated protein antibody status, the effect of which was mainly mediated by inflammation; however, the effect of valine at position 11 was also independent of the CRP level (P = 1.6 × 10(-4) ). Genetic markers of RA susceptibility located within HLA-DRB1 determine the levels of clinical and systemic inflammation independently, and also determine all objective measures of disease activity and outcome.es
dc.description.sponsorshipFunded by Arthritis Research UK. Grant Number: 20385 . National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit.es
dc.language.isoenges
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshRheumatology *
dc.subject.meshPeptides, Cyclic *
dc.subject.meshHealth Surveys *
dc.subject.meshAmino Acids *
dc.subject.meshC-Reactive Protein *
dc.subject.meshArginine *
dc.subject.meshPhenotype *
dc.subject.meshSeverity of Illness Index *
dc.subject.meshArthritis *
dc.subject.meshGenotype *
dc.subject.meshValine *
dc.subject.meshArthritis, Rheumatoid *
dc.subject.meshAntirheumatic Agents *
dc.subject.meshHaplotypes *
dc.subject.meshAlleles *
dc.subject.meshHLA-DRB1 Chains *
dc.subject.meshInflammation *
dc.titleHLA-DRB1 Amino Acid Positions 11/13, 71, and 74 Are Associated With Inflammation Level, Disease Activity, and the Health Assessment Questionnaire Score in Patients With Inflammatory Polyarthritis.es
dc.typeArtigoes
dc.identifier.doi10.1002/art.39780
dc.identifier.essn2326-5205
dc.identifier.pmid27274008
dc.issue.number11es
dc.journal.titleArthritis & rheumatology (Hoboken, N.J.)es
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Ferrol – Complexo Hospitalario Universitario de Ferrol::Reumatoloxíaes
dc.page.initial2618es
dc.page.final2628es
dc.relation.publisherversionhttp://onlinelibrary.wiley.com/doi/10.1002/art.39780/fulles
dc.rights.accessRightsopenAccesses
dc.subject.cie10Artritis reumatoide, no especificada es
dc.subject.decsencuestas de salud *
dc.subject.decsfenotipo *
dc.subject.decsvalina *
dc.subject.decsalelos *
dc.subject.decsarginina *
dc.subject.decsantirreumáticos *
dc.subject.decsinflamación *
dc.subject.decsíndice de gravedad de la enfermedad *
dc.subject.decsreumatología *
dc.subject.decscadenas HLA-DRB1 *
dc.subject.decsaminoácidos *
dc.subject.decsgenotipo *
dc.subject.decshaplotipos *
dc.subject.decspéptidos cíclicos *
dc.subject.decsartritis reumatoide *
dc.subject.decsproteína C reactiva *
dc.subject.decsartritis *
dc.subject.keywordartritis reumatoidees
dc.subject.keywordamino ácidoses
dc.subject.keywordcuestionarios de saludes
dc.subject.keywordgenéticaes
dc.subject.keywordantirreumáticoses
dc.subject.keywordProteína C-Reactivaes
dc.typefidesArtigo Científico (inclue Orixinal, Orixinal breve, Revisión Sistemática e Meta-análisis)es
dc.typesophosArtículo Originales
dc.volume.number68es


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