title: TGF beta1 polymorphisms are candidate predictors of the clinical response to rituximab in rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the association between several candidate single-nucleotide polymorphisms (SNPs) and responsiveness to rituximab in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Sixty-three RA patients were included. Nine genes (13 SNPs) were subsequently analyzed, including those coding for cytokines involved in synovitis (IL10, LTA, TGFβ1, TNF-α, TNF receptor II) and genes associated with RA susceptibility (-C5 TRAF1, STAT4, TNFAIP3 and PTPN22).
  
  
  RESULTS
  Forty-four patients were defined as responders and 19 as nonresponders. TGFβ1 Codon 10 and TGFβ1 Codon 25 SNPs were both associated with clinical response (probability to respond to treatment with the Codon 10C/T genotype: OR = 1.6; P = 0.002, and with the Codon 25 G/C genotype: OR = 1.6; P = 0.025). The probability to be a responder when the TGFβ Codon10 C/T and TGFβ Codon 25 G/C genotypes were co-inherited, doubled (OR = 2.6; P = 0.008).
  
  
  CONCLUSIONS
  The TGFβ1 SNPs are associated with a good response to rituximab therapy and as such could be useful genetic biomarkers in predicting therapy outcome.
authors: Inserm U844, Unité Génétique Clinique, Département Thérapeutique et Médecine Physique Ostéoarticulaire, CHU de Montpellier, 34295 Montpellier, France.
authors: Claire Immediato
authors: CI
authors: Daïen
authors: Sylvie
authors: S
authors: Fabre
authors: Cécile
authors: C
authors: Rittore
authors: Stephan
authors: S
authors: Soler
authors: Vincent
authors: V
authors: Daïen
authors: Gautier
authors: G
authors: Tejedor
authors: Doris
authors: D
authors: Cadart
authors: Nicolas
authors: N
authors: Molinari
authors: Jean-Pierre
authors: JP
authors: Daurès
authors: Christian
authors: C
authors: Jorgensen
authors: Isabelle
authors: I
authors: Touitou
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000069283:Rituximab; D050797:STAT4 Transcription Factor / Q000235:genetics; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D016896:Treatment Outcome; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D016207:Cytokines; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D047990:TNF Receptor-Associated Factor 1; D053773:Transforming Growth Factor beta1; D000069283:Rituximab; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3