The -308 tumour necrosis factor- gene polymorphism predicts therapeutic response to TNF -blockers in rheumatoid arthritis and spondyloarthritis patients
| Autor: | Peter M. Villiger, U Wirthmüller, Burkhard Möller, Michael Seitz |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male musculoskeletal diseases medicine.medical_specialty Genotype Arthritis Antibodies Monoclonal Humanized Severity of Illness Index Gastroenterology Receptors Tumor Necrosis Factor Etanercept Arthritis Rheumatoid Psoriatic arthritis Rheumatology Internal medicine medicine Adalimumab Humans Spondylitis Ankylosing Pharmacology (medical) Promoter Regions Genetic BASDAI Aged Ankylosing spondylitis Polymorphism Genetic Tumor Necrosis Factor-alpha business.industry Arthritis Psoriatic Antibodies Monoclonal Middle Aged Prognosis medicine.disease Infliximab Treatment Outcome Antirheumatic Agents Immunoglobulin G Rheumatoid arthritis Immunology Female business medicine.drug |
| Zdroj: | Rheumatology. 46:93-96 |
| ISSN: | 1462-0332 1462-0324 |
| Popis: | OBJECTIVE: To examine whether the G-to-A polymorphism at position -308 in the promoter of the tumour necrosis factor-alpha (TNFalpha) gene influences the therapeutic response to TNFalpha-blockers in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: A total of 54 patients with RA, 10 with PsA and 22 with AS were genotyped by polymerase chain reaction for the -308 TNFalpha promoter polymorphism. They were treated with infliximab (n = 63), adalimumab (n = 10) or etanercept (n = 13). Clinical response was assessed after 24 weeks by the Disease Activity Score in 28 joints (DAS28) for RA and PsA, and the Bath Ankylosing Spondylitis Activity Index (BASDAI) for AS patients. RESULTS: All patients with the A/A genotype (n = 3, all RA) and two patients with the A/G genotype (AS) failed to respond to anti-TNF treatment. Irrespective of the underlying disease, moderate response (n = 44) was predominantly associated with the A/G genotype (A/G 18/22, G/G 4/22), whereas good response (n = 59) was exclusively seen in patients with the G/G genotype. The average improvement in the DAS28 score was 0.83 in the A/A, 1.50 in the A/G and 2.64 in the G/G group of RA and PsA patients (P < 0.0001). The BASDAI score in AS improved on average by 1.21 in the A/G and by 3.30 in the G/G group (P < 0.005). CONCLUSIONS: The data suggest that humans with a TNFalpha -308 G/G genotype are better responders to anti-TNFalpha treatment than those with A/A or A/G genotypes independent of the treated rheumatic disease (RA, PsA or AS). |
| Databáze: | OpenAIRE |
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