TY - JOUR
T1 - Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients
AU - on behalf of the MATURA
AU - and PAMERA
AU - Consortia
AU - Taylor, John C.
AU - Bongartz, Tim
AU - Massey, Jonathan
AU - Mifsud, Borbala
AU - Spiliopoulou, Athina
AU - Scott, Ian C.
AU - Wang, Jianmei
AU - Morgan, Michael
AU - Plant, Darren
AU - Colombo, Marco
AU - Orchard, Peter
AU - Twigg, Sarah
AU - McInnes, Iain B.
AU - Porter, Duncan
AU - Freeston, Jane E.
AU - Nam, Jackie L.
AU - Cordell, Heather J.
AU - Isaacs, John D.
AU - Strathdee, Jenna L.
AU - Arnett, Donna
AU - de Hair, Maria J.H.
AU - Tak, Paul P.
AU - Aslibekyan, Stella
AU - van Vollenhoven, Ronald F.
AU - Padyukov, Leonid
AU - Bridges, S. Louis
AU - Pitzalis, Costantino
AU - Cope, Andrew P.
AU - Verstappen, Suzanne M.M.
AU - Emery, Paul
AU - Barnes, Michael R.
AU - Agakov, Felix
AU - McKeigue, Paul
AU - Mushiroda, Taisei
AU - Kubo, Michiaki
AU - Weinshilboum, Richard
AU - Barton, Anne
AU - Morgan, Ann W.
AU - Barrett, Jennifer H.
N1 - Publisher Copyright:
© 2018, Macmillan Publishers Limited, part of Springer Nature.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85046847176
U2 - 10.1038/s41397-018-0025-5
DO - 10.1038/s41397-018-0025-5
M3 - Review article
C2 - 29795407
AN - SCOPUS:85046847176
SN - 1470-269X
VL - 18
SP - 528
EP - 538
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
IS - 4
ER -