Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for
Adult
Aged
Antigens, CD
/ genetics
Antirheumatic Agents
/ therapeutic use
Apyrase
/ genetics
Arthritis, Rheumatoid
/ diagnosis
Biological Products
/ therapeutic use
CD40 Antigens
/ genetics
Cohort Studies
Female
Gene Expression Regulation
Genome-Wide Association Study
Humans
Male
Middle Aged
Molecular Targeted Therapy
/ methods
Multivariate Analysis
Predictive Value of Tests
Prognosis
Quantitative Trait Loci
/ genetics
Regression Analysis
Treatment Outcome
Tumor Necrosis Factor Inhibitors
/ therapeutic use
anti-tnf
pharmacogenetics
rheumatoid arthritis
Journal
Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
05
12
2018
revised:
11
04
2019
accepted:
11
04
2019
pubmed:
1
5
2019
medline:
13
3
2020
entrez:
1
5
2019
Statut:
ppublish
Résumé
We sought to investigate whether genetic effects on response to TNF inhibitors (TNFi) in rheumatoid arthritis (RA) could be localised by considering known genetic susceptibility loci for relevant traits and to evaluate the usefulness of these genetic loci for stratifying drug response. We studied the relation of TNFi response, quantified by change in swollen joint counts ( Δ SJC) and erythrocyte sedimentation rate ( Δ ESR) with locus-specific scores constructed from genome-wide assocation study summary statistics in 2938 genotyped individuals: 37 scores for RA; scores for 19 immune cell traits; scores for expression or methylation of 93 genes with previously reported associations between transcript level and drug response. Multivariate associations were evaluated in penalised regression models by cross-validation. We detected a statistically significant association between Δ SJC and the RA score at the The association with the CD39 trait is difficult to interpret because patients with RA are often prescribed TNFi after failing to respond to methotrexate. The CD39 and
Identifiants
pubmed: 31036624
pii: annrheumdis-2018-214877
doi: 10.1136/annrheumdis-2018-214877
pmc: PMC6669378
mid: NIHMS1043631
doi:
Substances chimiques
Antigens, CD
0
Antirheumatic Agents
0
Biological Products
0
CD40 Antigens
0
Tumor Necrosis Factor Inhibitors
0
Apyrase
EC 3.6.1.5
CD39 antigen
EC 3.6.1.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1055-1061Subventions
Organisme : Medical Research Council
ID : MR/K015346/1
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : U01 GM092691
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR070155
Pays : United States
Organisme : Arthritis Research UK
Pays : United Kingdom
Organisme : NIAMS NIH HHS
ID : R01 AR063759
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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