title: Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis.
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.
authors.affiliation: Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ferreiro-Iglesias
authors.affiliation: Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Montes
authors.affiliation: Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Perez-Pampin
authors.affiliation: Rheumatology Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain.
authors.forename: J D
authors.initials: JD
authors.lastname: Cañete
authors.affiliation: Department of Rheumatology, Hospital Clínico San Cecilio, Granada, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Raya
authors.affiliation: Department of Rheumatology, Hospital Clínico San Cecilio, Granada, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Magro-Checa
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
authors.forename: Y
authors.initials: Y
authors.lastname: Vasilopoulos
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
authors.forename: T
authors.initials: T
authors.lastname: Sarafidou
authors.affiliation: Rheumatology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Caliz
authors.affiliation: Rheumatology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Ferrer
authors.affiliation: Reumatology Department, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Joven
authors.affiliation: Reumatology Department, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Carreira
authors.affiliation: Department of Rheumatology and Institute for Health Research (IdiPAZ), University Hospital La Paz. Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Balsa
authors.affiliation: Immunology Unit, Instituto de Investigación Hospital Universitario La Paz, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.affiliation: 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.
authors.forename: F J
authors.initials: FJ
authors.lastname: Blanco
authors.affiliation: Department of Rheumatology, Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Moreno-Ramos
authors.affiliation: UGC de Reumatología, Instituto deInvestigación Biomédica de Málaga (IBIMA), HRU de Málaga, Universidad de Málaga, Málaga, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fernández-Nebro
authors.affiliation: UGC de Reumatología, Instituto deInvestigación Biomédica de Málaga (IBIMA), HRU de Málaga, Universidad de Málaga, Málaga, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Ordóñez
authors.affiliation: Department of Rheumatology, Hospital Doctor Peset, Valencia, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Alegre-Sancho
authors.affiliation: Department of Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Narváez
authors.affiliation: Rheumatology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Navarro-Sarabia
authors.affiliation: Rheumatology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Moreira
authors.affiliation: Rheumatology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Valor
authors.affiliation: Department of Rheumatology, Hospital Virgen de la Victoria, Málaga, Spain.
authors.forename: R
authors.initials: R
authors.lastname: García-Portales
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Marquez
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.affiliation: 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.
authors.forename: J J
authors.initials: JJ
authors.lastname: Gómez-Reino
authors.affiliation: Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-2624-0606
authors.initials: A
authors.lastname: Gonzalez
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics*; D000069285:Infliximab / Q000627:therapeutic use; D016753:Interleukin-10 / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000069285:Infliximab; C496559:CHUK protein, human; D051550:I-kappa B Kinase; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D000068879:Adalimumab