Genome-wide association study of response to tumour necrosis factor inhibitor therapy in rheumatoid arthritis.
Pharmacogenomics J
; 18(5): 657-664, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30166627
ABSTRACT
Rheumatoid arthritis (RA) is characterised by chronic synovial joint inflammation. Treatment has been revolutionised by tumour necrosis factor alpha inhibitors (TNFi) but each available drug shows a significant non-response rate. We conducted a genome-wide association study of 1752 UK RA TNFi-treated patients to identify predictors of change in the Disease Activity Score 28 (DAS28) and subcomponents over 3-6 months. The rs7195994 variant at the FTO gene locus was associated with infliximab response when looking at a change in the swollen joint count (SJC28) subcomponent (p = 9.74 × 10-9). Capture Hi-C data show chromatin interactions in GM12878 cells between rs2540767, in high linkage disequilibrium with rs7195994 (R2 = 0.9) and IRX3, a neighbouring gene of FTO. IRX3 encodes a transcription factor involved in adipocyte remodelling and is regarded as the obesity gene at the FTO locus. Importantly, the rs7195994 association remained significantly associated following adjustment for BMI. In addition, using capture Hi-C data we showed interactions between TNFi-response associated variants and 16 RA susceptibility variants.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Fator de Necrose Tumoral alfa
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Antirreumáticos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Pharmacogenomics J
Ano de publicação:
2018
Tipo de documento:
Article