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Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.
Cobb, J; Cule, E; Moncrieffe, H; Hinks, A; Ursu, S; Patrick, F; Kassoumeri, L; Flynn, E; Bulatovic, M; Wulffraat, N; van Zelst, B; de Jonge, R; Bohm, M; Dolezalova, P; Hirani, S; Newman, S; Whitworth, P; Southwood, T R; De Iorio, M; Wedderburn, L R; Thomson, W.
Afiliação
  • Cobb J; 1] Arthritis Research UK Centre for Genetics and Genomics, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK [2] NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manche
  • Cule E; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Moncrieffe H; Rheumatology Unit, UCL Institute of Child Health, London, UK.
  • Hinks A; Arthritis Research UK Centre for Genetics and Genomics, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
  • Ursu S; Rheumatology Unit, UCL Institute of Child Health, London, UK.
  • Patrick F; Rheumatology Unit, UCL Institute of Child Health, London, UK.
  • Kassoumeri L; Rheumatology Unit, UCL Institute of Child Health, London, UK.
  • Flynn E; Arthritis Research UK Centre for Genetics and Genomics, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
  • Bulatovic M; Department of Paediatric Immunology, University Medical Centre Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
  • Wulffraat N; Department of Paediatric Immunology, University Medical Centre Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
  • van Zelst B; Department of Clinical Chemistry, Erasmus University Medical Centre, Rotterdam, The Netherlands.
  • de Jonge R; Department of Clinical Chemistry, Erasmus University Medical Centre, Rotterdam, The Netherlands.
  • Bohm M; First Faculty of Medicine and General Faculty Hospital, Charles University in Prague, Praha, Czech Republic.
  • Dolezalova P; First Faculty of Medicine and General Faculty Hospital, Charles University in Prague, Praha, Czech Republic.
  • Hirani S; Centre for Health Services Research, School of Health Sciences, City University London, London, UK.
  • Newman S; Centre for Health Services Research, School of Health Sciences, City University London, London, UK.
  • Whitworth P; Institute of Child Health, Birmingham Children's Hospital, Birmingham, UK.
  • Southwood TR; Institute of Child Health, Birmingham Children's Hospital, Birmingham, UK.
  • De Iorio M; Department of Statistical Sciences, University College London, London, UK.
  • Wedderburn LR; 1] Rheumatology Unit, UCL Institute of Child Health, London, UK [2] Arthritis Research UK Centre for Adolescent Rheumatology, UCL Institute of Child Health, London, UK.
  • Thomson W; 1] Arthritis Research UK Centre for Genetics and Genomics, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK [2] NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manche
Pharmacogenomics J ; 14(4): 356-64, 2014 Aug.
Article em En | MEDLINE | ID: mdl-24709693
ABSTRACT
Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)) three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Juvenil / Metotrexato Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Juvenil / Metotrexato Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article