TGF beta1 polymorphisms are candidate predictors of the clinical response to rituximab in rheumatoid arthritis

Joint Bone Spine. 2012 Oct;79(5):471-5. doi: 10.1016/j.jbspin.2011.10.007. Epub 2011 Nov 29.

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).

Conclusion: The TGFβ1 SNPs are associated with a good response to rituximab therapy and as such could be useful genetic biomarkers in predicting therapy outcome.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics*
  • Case-Control Studies
  • Cytokines / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Pharmacogenetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Rituximab
  • STAT4 Transcription Factor / genetics
  • TNF Receptor-Associated Factor 1 / genetics
  • Transforming Growth Factor beta1 / genetics*
  • Treatment Outcome
  • Tumor Necrosis Factor alpha-Induced Protein 3

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Cytokines
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • TNF Receptor-Associated Factor 1
  • Transforming Growth Factor beta1
  • Rituximab
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3