Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis

Background Treatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatm...

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Veröffentlicht in:	Annals of the rheumatic diseases 2013-08, Vol.72 (8), p.1375-1381
Hauptverfasser:	Umiċeviċ Mirkov, Maša, Cui, Jing, Vermeulen, Sita H, Stahl, Eli A, Toonen, Erik J M, Makkinje, Remco R, Lee, Annette T, Huizinga, Tom W J, Allaart, Renee, Barton, Anne, Mariette, Xavier, Miceli, Corinne Richard, Criswell, Lindsey A, Tak, Paul P, de Vries, Niek, Saevarsdottir, Saedis, Padyukov, Leonid, Bridges, S Louis, van Schaardenburg, Dirk-Jan, Jansen, Tim L, Dutmer, Ellen A J, van de Laar, Mart A F J, Barrera, Pilar, Radstake, Timothy R D J, van Riel, Piet L C M, Scheffer, Hans, Franke, Barbara, Brunner, Han G, Plenge, Robert M, Gregersen, Peter K, Guchelaar, Henk-Jan, Coenen, Marieke J H
Format:	Artikel
Sprache:	eng
Schlagworte:	Adalimumab Anti-TNF Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized - therapeutic use Antirheumatic Agents - therapeutic use Apoptosis Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - genetics Arthritis, Rheumatoid - pathology Biomarkers Collaboration DNA Mutational Analysis Drug Resistance - genetics Etanercept Female Gene Expression Regulation Gene loci Gene Polymorphism Genetic Markers Genome-Wide Association Study Genomes Genomics Humans Immunoglobulin G - therapeutic use Inflammatory diseases Infliximab Male Medicin och hälsovetenskap Pharmacogenetics Polymorphism, Single Nucleotide Receptors, Tumor Necrosis Factor - therapeutic use Registries Rheumatism Rheumatoid Arthritis Rheumatology Studies TNF inhibitors Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor necrosis factor-TNF
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Zusammenfassung:	Background Treatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatment. This study was aimed at identifying genetic factors predicting anti-TNF treatment outcome in patients with RA using a genome-wide association approach. Methods We conducted a multistage, genome-wide association study with a primary analysis of 2 557 253 single-nucleotide polymorphisms (SNPs) in 882 patients with RA receiving anti-TNF therapy included through the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry and the database of Apotheekzorg. Linear regression analysis of changes in the Disease Activity Score in 28 joints after 14 weeks of treatment was performed using an additive model. Markers with p
ISSN:	0003-4967 1468-2060 1468-2060
DOI:	10.1136/annrheumdis-2012-202405