Effects of polymorphisms in TRAILR1 and TNFR1A on the response to anti-TNF therapies in patients with rheumatoid and psoriatic arthritis

Joint Bone Spine. 2012 Dec;79(6):591-6. doi: 10.1016/j.jbspin.2012.02.003. Epub 2012 Apr 4.


Objectives: As the role of polymorphisms in death receptors (DRs) such as Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptor 1 (TRAIL-R1) and Tumor Necrosis Factor Receptor 1A (TNF-R1A) on the response to anti-TNF therapy remains unknown, we evaluated the association between TRAILR1 and TNFR1A gene polymorphisms (rs20575/C626G and rs767455/G36A) and the pharmacogenetics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with TNFα blockers.

Methods: One hundred and forty-five patients (90 RA and 55 PsA) treated with anti-TNFα therapy (RA: 75 infliximab, 8 etanercept, 7 adalimumab. PsA: 27 infliximab, 19 etanercept, 9 adalimumab) were genotyped for TRAILR1 and TNFR1A polymorphisms by allelic discrimination. The response to anti-TNFα was assessed by EULAR criteria.

Results: In RA, the TRAILR1 CC genotype was associated with a better response after 3 and 6 months of anti-TNFα treatment (CC: 91.7% vs. CG/GG: 62.2%; P=0.019, and CC: 82.6% vs. CG/GG: 56.1%; P=0.019, respectively). Similar results were observed in only infliximab-treated RA patients. With respect to the TNFR1A polymorphism, there was an association between the AA genotype and a poorer response at 3 months in RA patients (AA: 39.3% vs.

Ag/gg: 19.0%; P=0.04). In PsA, TRAILR1 CC genotype was only associated with EULAR response to infliximab at 6 months (CC: 71.4% vs CG/GG: 50%P=0.048). In contrast to RA, the TNFR1 polymorphism in PsA was associated with a better response at 3 months (AA 88% vs AG/GG 58.9%; P=0.04).

Conclusions: This study provides the first evidence that a polymorphism in TRAILR1 influences the response to anti-TNFα therapy in RA and also suggests that TNFR1A polymorphism may have opposing effects on the response to anti-TNFα in RA and PsA.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Psoriatic / drug therapy*
  • Arthritis, Psoriatic / genetics
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Etanercept
  • Female
  • Follow-Up Studies
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Genetic / genetics*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics*
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Receptors, Tumor Necrosis Factor, Type I / genetics*
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept