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

on behalf of the MATURA, and PAMERA, Consortia

Research output: Contribution to journalReview article

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)528-538
Number of pages11
JournalPharmacogenomics Journal
Volume18
Issue number4
DOIs
Publication statusPublished - 01-07-2018

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Genome-Wide Association Study
Methotrexate
Rheumatoid Arthritis
Joints
Genome
Juvenile Arthritis
C-Reactive Protein
Single Nucleotide Polymorphism
Outcome Assessment (Health Care)
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

on behalf of the MATURA ; and PAMERA ; Consortia. / Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients. In: Pharmacogenomics Journal. 2018 ; Vol. 18, No. 4. pp. 528-538.
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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.",
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Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients. / on behalf of the MATURA; and PAMERA; Consortia.

In: Pharmacogenomics Journal, Vol. 18, No. 4, 01.07.2018, p. 528-538.

Research output: Contribution to journalReview article

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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 - Kubo, Michiaki

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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.

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JO - Pharmacogenomics Journal

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