Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis.
A Ferreiro-IglesiasA MontesE Perez-PampinJ D CañeteE RayaC Magro-ChecaY VasilopoulosT SarafidouR CalizM A FerrerB JovenP CarreiraA BalsaD Pascual-SalcedoF J BlancoM J Moreno-RamosA Fernández-NebroM C OrdóñezJ J Alegre-SanchoJ NarváezF Navarro-SarabiaV MoreiraL ValorR García-PortalesA MarquezJ MartinJ J Gómez-ReinoAntonio GonzálezPublished in: The pharmacogenomics journal (2015)
Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi. The most significant result was obtained with rs10919563 in PTPRC, which is a confirmed RA susceptibility locus. Its RA risk allele was associated with improved response (B=0.33, P=0.006). This is the second independent replication of this biomarker (P=9.08 × 10(-8) in the combined 3003 RA patients). In this way, PTPRC has become the most replicated genetic biomarker of response to TNFi. In addition, the positive but weaker replication of IL10 and CHUK should stimulate further validation studies.
Keyphrases
- rheumatoid arthritis
- end stage renal disease
- genome wide
- ejection fraction
- disease activity
- chronic kidney disease
- copy number
- prognostic factors
- peritoneal dialysis
- ankylosing spondylitis
- systemic lupus erythematosus
- dna methylation
- gene expression
- patient reported outcomes
- genome wide identification
- idiopathic pulmonary fibrosis