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Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.
Taylor, John C; Bongartz, Tim; Massey, Jonathan; Mifsud, Borbala; Spiliopoulou, Athina; Scott, Ian C; Wang, Jianmei; Morgan, Michael; Plant, Darren; Colombo, Marco; Orchard, Peter; Twigg, Sarah; McInnes, Iain B; Porter, Duncan; Freeston, Jane E; Nam, Jackie L; Cordell, Heather J; Isaacs, John D; Strathdee, Jenna L; Arnett, Donna; de Hair, Maria J H; Tak, Paul P; Aslibekyan, Stella; van Vollenhoven, Ronald F; Padyukov, Leonid; Bridges, S Louis; Pitzalis, Costantino; Cope, Andrew P; Verstappen, Suzanne M M; Emery, Paul; Barnes, Michael R; Agakov, Felix; McKeigue, Paul; Mushiroda, Taisei; Kubo, Michiaki; Weinshilboum, Richard; Barton, Anne; Morgan, Ann W; Barrett, Jennifer H.
Afiliação
  • Taylor JC; Leeds Institute of Cancer and Pathology, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
  • Bongartz T; Vanderbilt University, Nashville, TN, USA.
  • Massey J; Arthritis Research UK Centre for Genetics and Genomics, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
  • Mifsud B; NIHR Manchester BRC, Central Manchester Foundation Trust, Manchester, UK.
  • Spiliopoulou A; Clinical Pharmacology, William Harvey Research Institute, Queen Mary University, London, UK.
  • Scott IC; Centre for Population Health Sciences, Usher Institute, University of Edinburgh Old Medical School, Teviot Place, Edinburgh, UK.
  • Wang J; Pharmatics Ltd., 9, Little France Road, Edinburgh, UK.
  • Morgan M; Research Institute for Primary Care and Health Sciences, Primary Care Sciences, Keele University and Department of Rheumatology, Haywood Hospital, High Lane, Burslem, Staffordshire, UK.
  • Plant D; Department of Medical and Molecular Genetics, King's College London, London, UK.
  • Colombo M; Roche Products, Welwyn Garden City, UK.
  • Orchard P; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
  • Twigg S; Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK.
  • McInnes IB; Arthritis Research UK Centre for Genetics and Genomics, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
  • Porter D; NIHR Manchester BRC, Central Manchester Foundation Trust, Manchester, UK.
  • Freeston JE; Centre for Population Health Sciences, Usher Institute, University of Edinburgh Old Medical School, Teviot Place, Edinburgh, UK.
  • Nam JL; Pharmatics Ltd., 9, Little France Road, Edinburgh, UK.
  • Cordell HJ; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
  • Isaacs JD; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
  • Strathdee JL; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
  • Arnett D; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
  • de Hair MJH; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
  • Tak PP; Institute of Genetic Medicine, Newcastle University, Newcastle, UK.
  • Aslibekyan S; Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University and NIHR Newcastle Biomedical Research Centre in Ageing and Long Term Conditions, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • van Vollenhoven RF; Leeds Institute of Cancer and Pathology, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
  • Padyukov L; University of Kentucky College of Public Health, Lexington, KY, 40536, USA.
  • Bridges SL; University Medical Center Utrecht, Utrecht, The Netherlands.
  • Pitzalis C; Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
  • Cope AP; GlaxoSmithKline, Stevenage, UK.
  • Verstappen SMM; Cambridge University, Cambridge, UK.
  • Emery P; Ghent University, Ghent, Belgium.
  • Barnes MR; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Agakov F; Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • McKeigue P; Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • Mushiroda T; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Kubo M; Barts and The London School of Medicine & Dentistry, William Harvey Research Institute, Queen Mary University, London, UK.
  • Weinshilboum R; Academic Department of Rheumatology, Faculty of Life Sciences and Medicine, King's College London, London, UK.
  • Barton A; Arthritis Research UK Centre for Genetics and Genomics, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
  • Morgan AW; NIHR Manchester BRC, Central Manchester Foundation Trust, Manchester, UK.
  • Barrett JH; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Pharmacogenomics J ; 18(4): 528-538, 2018 07.
Article em En | MEDLINE | ID: mdl-29795407
Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10-7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Metotrexato / Antirreumáticos / Estudo de Associação Genômica Ampla Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Pharmacogenomics J Assunto da revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Metotrexato / Antirreumáticos / Estudo de Associação Genômica Ampla Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Pharmacogenomics J Assunto da revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Ano de publicação: 2018 Tipo de documento: Article