Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.
Pharmacogenomics J
; 18(4): 528-538, 2018 07.
Article
en En
| MEDLINE
| ID: mdl-29795407
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Metotrexato
/
Antirreumáticos
/
Estudio de Asociación del Genoma Completo
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Pharmacogenomics J
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido