title: TRAF1/C5 but not PTPRC variants are potential predictors of rheumatoid arthritis response to anti-tumor necrosis factor therapy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Edifício Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Avenida Egas Moniz, 1649-028 Lisbon, Portugal ; Rheumatology Department, Hospital de Santa Maria (CHLN), Lisbon Academic Medical Centre, 1649-035 Lisbon, Portugal ; Division of Rheumatology, Allergy and Immunology, Section of Clinical Sciences, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Helena
authors.identifier: 0000-0003-1894-4870
authors.initials: H
authors.lastname: Canhão
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Edifício Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Avenida Egas Moniz, 1649-028 Lisbon, Portugal ; Rheumatology Department, Hospital de Santa Maria (CHLN), Lisbon Academic Medical Centre, 1649-035 Lisbon, Portugal.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Rodrigues
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Edifício Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Avenida Egas Moniz, 1649-028 Lisbon, Portugal ; Rheumatology Department, Hospital Garcia de Orta, 2805-267 Almada, Portugal.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Santos
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Edifício Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Avenida Egas Moniz, 1649-028 Lisbon, Portugal.
authors.forename: Diana
authors.identifier: 0000-0002-1015-3946
authors.initials: D
authors.lastname: Carmona-Fernandes
authors.affiliation: SEEBMO, Hospital de Santo Espirito da Ilha Terceira, Azores, 9700-049 Angra do Heroísmo, Portugal ; Genetics & Arthritis Research Group (GARG), Institute for Molecular and Cell Biology (IBMC), 4150-180 Oporto, Portugal.
authors.forename: Bruno F
authors.initials: BF
authors.lastname: Bettencourt
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Section of Clinical Sciences, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.affiliation: SEEBMO, Hospital de Santo Espirito da Ilha Terceira, Azores, 9700-049 Angra do Heroísmo, Portugal ; Genetics & Arthritis Research Group (GARG), Institute for Molecular and Cell Biology (IBMC), 4150-180 Oporto, Portugal.
authors.forename: Fabiana L
authors.initials: FL
authors.lastname: Rocha
authors.affiliation: Rheumatology Department, Hospital Garcia de Orta, 2805-267 Almada, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Canas Silva
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Edifício Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Avenida Egas Moniz, 1649-028 Lisbon, Portugal ; Rheumatology Department, Hospital de Santa Maria (CHLN), Lisbon Academic Medical Centre, 1649-035 Lisbon, Portugal.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Polido-Pereira
authors.affiliation: Rheumatology Department, Hospital de Santa Maria (CHLN), Lisbon Academic Medical Centre, 1649-035 Lisbon, Portugal.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Pereira Silva
authors.affiliation: Rheumatology Department, Conde de Bertiandos Hospital (ULSAM), 4990-041 Ponte de Lima, Portugal.
authors.forename: José António
authors.initials: JA
authors.lastname: Costa
authors.affiliation: Rheumatology Department, Conde de Bertiandos Hospital (ULSAM), 4990-041 Ponte de Lima, Portugal.
authors.forename: Domingos
authors.initials: D
authors.lastname: Araujo
authors.affiliation: Instituto Português de Reumatologia, Lisbon, Portugal.
authors.forename: Cândida
authors.initials: C
authors.lastname: Silva
authors.affiliation: Instituto Português de Reumatologia, Lisbon, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Santos
authors.affiliation: Rheumatology Department, Centro Hospitalar da Universidade de Coimbra, 3000-076 Coimbra, Portugal.
authors.forename: Cátia
authors.initials: C
authors.lastname: Duarte
authors.affiliation: Rheumatology Department, Virgen de las Nieves University Hospital, Granada, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cáliz
authors.affiliation: Rheumatology Department, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.
authors.forename: Ileana
authors.initials: I
authors.lastname: Filipescu
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal ; Rheumatology Department, Hospital de Egas Moniz (CHLO), 1349-019 Lisbon, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pimentel-Santos
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal ; Rheumatology Department, Hospital de Egas Moniz (CHLO), 1349-019 Lisbon, Portugal.
authors.forename: Jaime
authors.initials: J
authors.lastname: Branco
authors.affiliation: Genomic Oncology Area, GENYO Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sainz
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Section of Clinical Sciences, Brigham and Women's Hospital, Boston, MA 02115, USA ; The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Section of Clinical Sciences, Brigham and Women's Hospital, Boston, MA 02115, USA ; Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.affiliation: SEEBMO, Hospital de Santo Espirito da Ilha Terceira, Azores, 9700-049 Angra do Heroísmo, Portugal ; Genetics & Arthritis Research Group (GARG), Institute for Molecular and Cell Biology (IBMC), 4150-180 Oporto, Portugal.
authors.forename: Jácome
authors.initials: J
authors.lastname: Bruges-Armas
authors.affiliation: Rheumatology Department, Centro Hospitalar da Universidade de Coimbra, 3000-076 Coimbra, Portugal.
authors.forename: José António P
authors.initials: JA
authors.lastname: Da Silva
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Edifício Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Avenida Egas Moniz, 1649-028 Lisbon, Portugal ; Rheumatology Department, Hospital de Santa Maria (CHLN), Lisbon Academic Medical Centre, 1649-035 Lisbon, Portugal.
authors.forename: João Eurico
authors.initials: JE
authors.lastname: Fonseca
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Section of Clinical Sciences, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000483:Alleles; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000068800:Etanercept / Q000008:administration & dosage; D056726:Genetic Association Studies; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage; D017493:Leukocyte Common Antigens / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D059811:HLA-DRB1 Chains; D047990:TNF Receptor-Associated Factor 1; C529000:golimumab; D000069285:Infliximab; D017493:Leukocyte Common Antigens; C516765:PTPN22 protein, human; C516769:PTPRC protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D000068879:Adalimumab; D000068800:Etanercept
references.citation: Ann Rheum Dis. 2010 Jun;69(6):1022-8
references.pmid: 19966089
references.citation: Arthritis Rheum. 2010 Jan;62(1):22-32
references.pmid: 20039405
references.citation: Arthritis Res Ther. 2010;12(2):R38
references.pmid: 20205706
references.citation: Arthritis Res Ther. 2010;12(2):R57
references.pmid: 20353580
references.citation: Arthritis Rheum. 2010 Jul;62(7):1849-61
references.pmid: 20309874
references.citation: Ann Rheum Dis. 2011 Apr;70(4):711-2
references.pmid: 20876593
references.citation: Acta Reumatol Port. 2011 Jan-Mar;36(1):45-56
references.pmid: 21483280
references.citation: N Engl J Med. 2011 Dec 8;365(23):2205-19
references.pmid: 22150039
references.citation: Arthritis Rheum. 2012 Mar;64(3):665-70
references.pmid: 21952740
references.citation: Acta Reumatol Port. 2011 Oct-Dec;36(4):385-8
references.pmid: 22472929
references.citation: Rheumatology (Oxford). 2012 Nov;51(11):2020-6
references.pmid: 22843791
references.citation: PLoS Genet. 2013 Mar;9(3):e1003394
references.pmid: 23555300
references.citation: Arthritis Res Ther. 2014;16(4):414
references.pmid: 25138370
references.citation: Lancet. 1999 Dec 4;354(9194):1932-9
references.pmid: 10622295
references.citation: J Immunol. 2000 Apr 15;164(8):4340-7
references.pmid: 10754334
references.citation: Reumatismo. 2002;54(1):19-26
references.pmid: 12089610
references.citation: Ann Rheum Dis. 2003 Jun;62(6):526-9
references.pmid: 12759288
references.citation: Arthritis Rheum. 2004 Apr;50(4):1077-82
references.pmid: 15077289
references.citation: Arthritis Rheum. 2004 Sep;50(9):2750-6
references.pmid: 15457442
references.citation: Arthritis Rheum. 1988 Mar;31(3):315-24
references.pmid: 3358796
references.citation: Cell. 1994 Aug 26;78(4):681-92
references.pmid: 8069916
references.citation: Arthritis Rheum. 1996 Jan;39(1):34-40
references.pmid: 8546736
references.citation: Ann Rheum Dis. 1998 Apr;57(4):209-13
references.pmid: 9709176
references.citation: Ann Rheum Dis. 2005 May;64(5):793-4
references.pmid: 15834068
references.citation: Am J Hum Genet. 2005 Dec;77(6):1044-60
references.pmid: 16380915
references.citation: Rheumatology (Oxford). 2006 Dec;45(12):1558-65
references.pmid: 16705046
references.citation: Ann Rheum Dis. 2007 Feb;66(2):246-8
references.pmid: 16793843
references.citation: Nature. 2007 Jun 7;447(7145):661-78
references.pmid: 17554300
references.citation: J Rheumatol. 2007 Aug;34(8):1670-3
references.pmid: 17611987
references.citation: N Engl J Med. 2007 Sep 20;357(12):1199-209
references.pmid: 17804836
references.citation: PLoS Med. 2007 Sep;4(9):e278
references.pmid: 17880261
references.citation: Rheumatology (Oxford). 2007 Dec;46(12):1842-4
references.pmid: 18032542
references.citation: Nat Genet. 2007 Dec;39(12):1431-3
references.pmid: 17982455
references.citation: Arthritis Res Ther. 2008;10(1):R26
references.pmid: 18307784
references.citation: Hum Mol Genet. 2008 Aug 1;17(15):2274-9
references.pmid: 18434327
references.citation: Ann Rheum Dis. 2009 Jan;68(1):69-74
references.pmid: 18375541
references.citation: Arthritis Rheum. 2009 Jan;60(1):39-46
references.pmid: 19116907
references.citation: Nat Rev Rheumatol. 2009 Oct;5(10):578-82
references.pmid: 19798034
references.citation: Nat Genet. 2010 Jun;42(6):508-14
references.pmid: 20453842