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; Bulatović, M; Wulffraat, N; +14 more...van Zelst, B; de Jonge, R; Bohm, M; Dolezalova, P; Hirani, S; Newman, S; Whitworth, P; Southwood, T; De Iorio, M; Childhood Arthritis Response to Medication Study (CHARMS); Childhood Arthritis Prospective Study (CAPS); BSPAR study group; Wedderburn, L; Thomson, W and (2013) Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases. The pharmacogenomics journal, 14 (4). pp. 356-364. ISSN 1470-269X DOI: 10.1038/tpj.2014.3
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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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Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.pdf
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