Effects of polymorphisms in TRAILR1 and TNFR1A on the response to anti-TNF therapies in patients with rheumatoid and psoriatic arthritis - 05/12/12
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Abstract |
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 TNF⍺ blockers.
Methods |
One hundred and forty-five patients (90 RA and 55 PsA) treated with anti-TNF⍺ 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-TNF⍺ 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-TNF⍺ 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-TNF⍺ therapy in RA and also suggests that TNFR1A polymorphism may have opposing effects on the response to anti-TNF⍺ in RA and PsA.
Le texte complet de cet article est disponible en PDF.Keywords : Rheumatoid arthritis, Psoriatic arthritis, Pharmacogenetics, TRAILR1 and TNFR1A polymorphism, Anti-TNFalpha
Plan
Vol 79 - N° 6
P. 591-596 - décembre 2012 Retour au numéro
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