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., van Zelst, B., de Jonge, R., Bohm, M., Dolezalova, P., Hirani, S. P., Newman, S. P., Whitworth, P., Southwood, T., De Iorio, M., Childhood Arthritis Response to Medication Study (CHARMS), ., Childhood Arthritis Prospective Study (CAPS), ., BSPAR study group, ., Wedderburn, L. R. & Thomson, W. (2014). Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases. The Pharmacogenomics Journal, doi: 10.1038/tpj.2014.3

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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 (Po0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (Po1105): 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.

Item Type: Article
Additional Information: Article in press.
Uncontrolled Keywords: juvenile idiopathic arthritis, methotrexate, pharmacogenetics, response
Subjects: R Medicine > RC Internal medicine
Divisions: School of Health Sciences > Healthcare Research Unit
Related URLs:
URI: http://openaccess.city.ac.uk/id/eprint/3784

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