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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; ... Thomson, W; + view all (2014) Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases. Pharmacogenomics Journal , 14 (4) pp. 356-364. 10.1038/tpj.2014.3. Green open access

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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.The Pharmacogenomics Journal advance online publication, 8 April 2014; doi:10.1038/tpj.2014.3.

Type: Article
Title: Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/tpj.2014.3
Publisher version: http://dx.doi.org/10.1038/tpj.2014.3
Additional information: © 2014 Macmillan Publishers Limited. All Rights Reserved. This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/.
Keywords: juvenile idiopathic arthritis; methotrexate; pharmacogenetics; response
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Statistical Science
URI: https://discovery.ucl.ac.uk/id/eprint/1426791
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