Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases

J Cobb, E Cule, H Moncrieffe, A Hinks, S Ursu, F Patrick, L Kassoumeri, E Flynn, M Bulatovic, N Wulffraat, Bertrand van Zelst, R Jonge, M Bohm, P Dolezalova, S Hirani, S Newman, P Whitworth, TR Southwood, M De Iorio, LR WedderburnW Thomson

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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 x 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.
Original languageUndefined/Unknown
Pages (from-to)356-364
Number of pages9
JournalPharmacogenomics Journal
Volume14
Issue number4
DOIs
Publication statusPublished - 2014

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