title: Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid arthritis and response to anti-TNF drugs: a multicenter study.
abstract: BACKGROUND
  Recent research suggests that genetic variants in the tumor necrosis factor receptor 2 (TNFRSF1B) gene may have an impact on susceptibility to rheumatoid arthritis (RA) and drug response. The present population-based case-control study was carried out to evaluate whether 5 tagging single-nucleotide polymorphisms (SNPs) within the TNFRSF1B gene are associated with the risk of RA and response to antitumor necrosis factor (TNF) drugs.
  
  
  METHODS
  The study population included 1412 RA patients and 1225 healthy controls. A subset of 596 anti-TNF-naive RA patients was selected to assess the association of TNFRSF1B SNPs and drug response according to the EULAR response criteria.
  
  
  RESULTS
  We found that carriers of the TNFRSF1Brs3397C allele had a significantly increased risk of developing RA (P=0.0006). Importantly, this association remained significant after correction for multiple testing. We also confirmed the lack of association of the TNFRSF1Brs1061622 SNP with the risk of RA in the single-SNP analysis (P=0.89), but also through well-powered meta-analyses (PDOM=0.67 and PREC=0.37, respectively). In addition, our study showed that carriers of the TNFRSF1Brs3397C/C, TNFRSF1Brs1061622G/G, and TNFRSF1Brs1061631A/A genotypes had an increased risk of having a worse response to anti-TNF drugs at the level of P less than 0.05 (P=0.014, 0.0085 and 0.028, respectively). We also observed that, according to a log-additive model, carriers of the TNFRSF1Brs3397C or TNFRSF1Brs1061622G alleles showed an increased risk of having worse response to anti-TNF medications (P=0.018 and 0.0059). However, the association of the TNFRSF1Brs1061622 SNP only reached marginal significance after correction for multiple testing according to a log-additive model (P=0.0059) and it was not confirmed through a meta-analysis (PDOM=0.12).
  
  
  CONCLUSIONS
  Our results suggest that the TNFRSF1Brs3397 variant may play a role in modulating the risk of RA, but does not provide strong evidence of an impact of TNFRSF1B variants in determining response to anti-TNF drugs.
authors: aGenomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada Departments of bImmunology cRheumatology, Virgen de las Nieves University Hospital, Granada dRheumatology Department, Reina Sofía Hospital, IMIBIC, University of Córdoba, Córdoba eRheumatology Unit, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain fRheumatology Research Unit, Molecular Medicine Institute, Medicine Faculty of Lisbon University gRheumatology Department, Santa Maria Hospital - CHLN, Lisbon, Portugal hRheumatology Department, University of Medicine and Pharmacy 'Iuliu Hatieganu' Cluj-Napoca, Romania.
authors: Luz M
authors: LM
authors: Canet
authors: Ileana
authors: I
authors: Filipescu
authors: Rafael
authors: R
authors: Cáliz
authors: Carmen B
authors: CB
authors: Lupiañez
authors: Helena
authors: H
authors: Canhão
authors: Alejandro
authors: A
authors: Escudero
authors: Juana
authors: J
authors: Segura-Catena
authors: María J
authors: MJ
authors: Soto-Pino
authors: Miguel A
authors: MA
authors: Ferrer
authors: Antonio
authors: A
authors: García
authors: Lurdes
authors: L
authors: Romani
authors: Eva
authors: E
authors: Pérez-Pampin
authors: Alfonso
authors: A
authors: González-Utrilla
authors: Miguel A
authors: MA
authors: López Nevot
authors: Eduardo
authors: E
authors: Collantes
authors: João E
authors: JE
authors: Fonseca
authors: Juan
authors: J
authors: Sainz
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D047889:Receptors, Tumor Necrosis Factor, Type II; C439524:TNF protein, human; C415902:TNFRSF1B protein, human; D014409:Tumor Necrosis Factor-alpha