Taylor, JC, Bongartz, T, Massey, J, Mifsud, B, Spiliopoulou, A, Scott, IC, Wang, J, Morgan, M, Plant, D and Colombo, M (2018) Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients. Pharmacogenomics Journal, 18. pp. 528-538. ISSN 1473-1150

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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 = 10−7 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: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Nature Publishing Group at http://doi.org/10.1038/s41397-018-0025-5 - please refer to any applicable terms of use of the publisher.
Subjects: R Medicine > RC Internal medicine > RC925 Diseases of the musculoskeletal system
Divisions: Faculty of Medicine and Health Sciences > Primary Care Health Sciences
Depositing User: Symplectic
Date Deposited: 08 Jun 2018 15:26
Last Modified: 28 Feb 2019 15:11
URI: https://eprints.keele.ac.uk/id/eprint/5005

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