Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients

Taylor, J. C. et al. (2018) Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients. Pharmacogenomics Journal, 18(4), pp. 528-538. (doi: 10.1038/s41397-018-0025-5) (PMID:29795407)

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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 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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Porter, Dr Duncan
Authors: Taylor, J. C., Bongartz, T., Massey, J., Mifsud, B., Spiliopoulou, A., Scott, I. C., Wang, J., Morgan, M., Plant, D., Colombo, M., Orchard, P., Twigg, S., McInnes, I. B., Porter, D., Freeston, J. E., Nam, J. L., Cordell, H. J., Isaacs, J. D., Strathdee, J. L., Arnett, D., de Hair, M. J. H., Tak, P. P., Aslibekyan, S., van Vollenhoven, R. F., Padyukov, L., Bridges, S. L., Pitzalis, C., Cope, A. P., Verstappen, S. M. M., Emery, P., Barnes, M. R., Agakov, F., McKeigue, P., Mushiroda, T., Kubo, M., Weinshilboum, R., Barton, A., Morgan, A. W., and Barrett, J. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Pharmacogenomics Journal
Publisher:Nature Publishing Group
ISSN (Online):1473-1150
Published Online:25 May 2018
Copyright Holders:Copyright © 2018 Macmillan Publishers Limited, part of Springer Nature
First Published:First published in Pharmacogenomics Journal 18(4): 528-538
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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