1. TRAF1/C5 but Not PTPRC Variants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy
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Helena Canhão, Jácome Bruges-Armas, Daniel H. Solomon, Joaquim Polido-Pereira, Cátia Duarte, Robert M. Plenge, Domingos Araújo, João Eurico Fonseca, Ana M. Rodrigues, Jaime Branco, Rafael Cáliz, José António Costa, Diana Carmona-Fernandes, Jing Cui, José Canas da Silva, I. Filipescu, Cândida Silva, Fernando Pimentel-Santos, José Alberto Pereira da Silva, Helena Santos, Fabiana L. Rocha, Elizabeth W. Karlson, Juan Sainz, Maria José Santos, Bruno Filipe Bettencourt, José António Pereira da Silva, Repositório da Universidade de Lisboa, [Canhão,H, Rodrigues,AM, Santos,MJ, Carmona-Fernandes,D, Polido-Pereira,J, Fonseca,JE] Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. [Canhão,H, Polido-Pereira,JA, Pereira Silva,JA, Fonseca,JE] Rheumatology Department, Hospital de Santa Maria (CHLN), Lisbon Academic Medical Centre, Lisbon, Portugal. [Canhão,H, Cui,J, Plenge,RM, Solomon,DH, Karlson,EW] Division of Rheumatology, Allergy and Immunology, Section of Clinical Sciences, Brigham and Women’s Hospital, Boston, USA. [Santos,MJ, Canas Silva,J] Rheumatology Department, Hospital Garcia de Orta, Almada, Portugal. [Bettencourt,BF, Rocha,FL, Bruges-Armas,J] SEEBMO, Hospital de Santo Espirito da Ilha Terceira, Azores, Portugal. [Bettencourt,BF, Bruges-Armas,J] Genetics & Arthritis Research Group (GARG), Institute for Molecular and Cell Biology (IBMC), Oporto, Portugal. [Costa,JA, Araujo,D] Rheumatology Department, Conde de Bertiandos Hospital (ULSAM), Ponte de Lima, Portugal. [Silva,C, Santos,H] Instituto Português de Reumatologia, Lisbon, Portugal. [Duarte,C, Da Silva,JAP] Rheumatology Department, Centro Hospitalar da Universidade de Coimbra, Coimbra, Portugal. [Cáliz,R] Rheumatology Department, Virgen de las Nieves University Hospital, Granada, Spain. [Filipescu,I] Rheumatology Department, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania. [Pimentel-Santos,F, Branco,J] CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal. Rheumatology Department, Hospital de Egas Moniz (CHLO), Lisbon, Portugal. [Sainz,J] Genomic Oncology Area, GENYO Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. [Plenge,RM] The Broad Institute of Harvard and MIT, Cambridge, MA, USA. [Solomon,DH] Division of Pharmacoepidemiology, Brigham and Women’s Hospital, Boston, MA, USA., This work was supported by a grant from Harvard-Portugal Program HMSP-ICS/SAU-ICT/0002/2010. Daniel H. Solomon received support for this work from the NIH (K24-AR-055989). Elizabeth W. Karlson received support for this work from NIH (K24-AR-AR0524). Reuma.pt received unrestricted grants from Abbott, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, Roche, and UCB Pharma., NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Centro de Estudos de Doenças Crónicas (CEDOC)
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Oncology ,Southern European ,Anti-tumor necrosis factor (anti-TNF) ,lcsh:Medicine ,Genome-wide association study ,SUSCEPTIBILITY ,Logistic regression ,Etanercept ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Arthritis, Rheumatoid ,Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Group [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Logistic Models [Medical Subject Headings] ,HLA-DRB1 ,PTPRC locus ,education.field_of_study ,biology ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,Modelos logísticos ,3. Good health ,METHOTREXATE ,Humanos ,Diseases::Musculoskeletal Diseases::Rheumatic Diseases::Arthritis, Rheumatoid [Medical Subject Headings] ,Antirreumáticos ,Rheumatoid arthritis ,DISEASES ,Alelos ,medicine.drug ,Research Article ,Adult ,medicine.medical_specialty ,Article Subject ,Population ,Artritis reumatoide ,PTPRC ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antirheumatic Agents [Medical Subject Headings] ,Internal medicine ,Immunology and Microbiology(all) ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors::Tumor Necrosis Factor-alpha [Medical Subject Headings] ,medicine ,ETANERCEPT ,Humans ,Grupo de ascendencia continental europea ,GENOME-WIDE ASSOCIATION ,education ,Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings] ,Alleles ,Genetic Association Studies ,REGISTER ,Aged ,General Immunology and Microbiology ,Factor 1 asociado a receptor de TNF ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,lcsh:R ,Adalimumab ,Protein Tyrosine Phosphatase, Non-Receptor Type 22 ,REMISSION ,medicine.disease ,TNF Receptor-Associated Factor 1 ,POLYMORPHISM ,Infliximab ,Factor de necrosis tumoral alfa ,Minor allele frequency ,Immunology ,biology.protein ,Leukocyte Common Antigens ,business ,ALPHA THERAPY ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Adaptor Proteins, Signal Transducing::Tumor Necrosis Factor Receptor-Associated Peptides and Proteins::TNF Receptor-Associated Factor 1 [Medical Subject Headings] ,HLA-DRB1 Chains - Abstract
Copyright © 2015 Helena Canhão et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., Background: The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. Methods: We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. Results: No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. Conclusion: This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response., This work was supported by a grant from Harvard-Portugal Program HMSP-ICS/SAU-ICT/0002/2010. Daniel H. Solomon received support for this work from the NIH (K24-AR-055989). Elizabeth W. Karlson received support for this work from NIH (K24-AR-AR0524). Reuma.pt received unrestricted grants from Abbott, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, Roche, and UCB Pharma.
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- 2015
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