| Literature DB >> 29795407 |
John C Taylor1, Tim Bongartz2, Jonathan Massey3,4, Borbala Mifsud5, Athina Spiliopoulou6,7, Ian C Scott8,9, Jianmei Wang10, Michael Morgan11,12, Darren Plant3,4, Marco Colombo6, Peter Orchard7, Sarah Twigg11, Iain B McInnes13, Duncan Porter13, Jane E Freeston11, Jackie L Nam11, Heather J Cordell14, John D Isaacs15, Jenna L Strathdee1, Donna Arnett16, Maria J H de Hair17, Paul P Tak18,19,20,21, Stella Aslibekyan22, Ronald F van Vollenhoven23, Leonid Padyukov23, S Louis Bridges22, Costantino Pitzalis24, Andrew P Cope25, Suzanne M M Verstappen3,4, Paul Emery11, Michael R Barnes24, Felix Agakov7, Paul McKeigue6, Taisei Mushiroda26, Michiaki Kubo26, Richard Weinshilboum27, Anne Barton3,4, Ann W Morgan28, Jennifer H Barrett1.
Abstract
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.Entities:
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Year: 2018 PMID： 29795407 DOI： 10.1038/s41397-018-0025-5
Source DB: PubMed Journal: Pharmacogenomics J ISSN： 1470-269X Impact factor: 3.550