Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis
Por:
Ferreiro-Iglesias A, Montes A, Perez-Pampin E, Cañete JD, Raya E, Magro-Checa C, Vasilopoulos Y, Sarafidou T, Caliz R, Ferrer MA, Joven B, Carreira P, Balsa A, Pascual-Salcedo D, Blanco FJ, Moreno-Ramos MJ, Fernández-Nebro A, Ordóñez MC, Alegre-Sancho JJ, Narváez J, Navarro-Sarabia F, Moreira V, Valor L, García-Portales R, Marquez A, Martin J, Gómez-Reino JJ and Gonzalez A
Publicada:
1 abr 2016
Resumen:
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 x 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.
Filiaciones:
Ferreiro-Iglesias A:
Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain
Montes A:
Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain
Perez-Pampin E:
Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain
Cañete JD:
Rheumatology Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain
Raya E:
Department of Rheumatology, Hospital Clínico San Cecilio, Granada, Spain
Magro-Checa C:
Department of Rheumatology, Hospital Clínico San Cecilio, Granada, Spain
Vasilopoulos Y:
Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece
Sarafidou T:
Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece
Caliz R:
Rheumatology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain
Ferrer MA:
Rheumatology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain
Joven B:
Reumatology Department, Hospital 12 de Octubre, Madrid, Spain
Carreira P:
Reumatology Department, Hospital 12 de Octubre, Madrid, Spain
Balsa A:
Department of Rheumatology and Institute for Health Research (IdiPAZ), University Hospital La Paz. Madrid, Spain
Pascual-Salcedo D:
Immunology Unit, Instituto de Investigación Hospital Universitario La Paz, Hospital Universitario La Paz, Madrid, Spain
Blanco FJ:
Servicio de Reumatología. Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain
Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
Moreno-Ramos MJ:
Department of Rheumatology, Hospital Virgen de la Arrixaca, Murcia, Spain
Fernández-Nebro A:
UGC de Reumatología, Instituto deInvestigación Biomédica de Málaga (IBIMA), HRU de Málaga, Universidad de Málaga, Málaga, Spain
Ordóñez MC:
UGC de Reumatología, Instituto deInvestigación Biomédica de Málaga (IBIMA), HRU de Málaga, Universidad de Málaga, Málaga, Spain
:
Department of Rheumatology, Hospital Doctor Peset, Valencia, Spain
Narváez J:
Department of Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain
Navarro-Sarabia F:
Rheumatology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain
Moreira V:
Rheumatology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain
Valor L:
Rheumatology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
García-Portales R:
Department of Rheumatology, Hospital Virgen de la Victoria, Málaga, Spain
Marquez A:
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain
Martin J:
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain
Gómez-Reino JJ:
Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain
Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
Gonzalez A:
Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain
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