Abstract
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.
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Acknowledgements
We thank Carmen Pena-Pena for technical assistance and Manuel Calaza for help with data management. We also thank Arturo R de la Serna and Berta Magallares of the Hospital Santa Creu e San Pau (Barcelona, Spain) for providing samples. Funding was provided by grants PI11/01048, PI12/01909 and by RETICS Program, RD12/0009/0008 and RD12/0009/0004 (RIER) of the Instituto de Salud Carlos III (Spain) that are partially financed by the European Regional Development Fund of the European Union.
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Ferreiro-Iglesias, A., Montes, A., Perez-Pampin, E. et al. Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis. Pharmacogenomics J 16, 137–140 (2016). https://doi.org/10.1038/tpj.2015.29
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DOI: https://doi.org/10.1038/tpj.2015.29
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