Tumor Necrosis Factor–α Promoter −308/238 Polymorphism Association with Less Severe Disease in Ankylosing Spondylitis is Unrelated to Serum TNF-α and Does Not Predict TNF Inhibitor Response
| Autor: | Gunnstein Bakland, Sylvia Sagen-Johnsen, Johannes C. Nossent |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype medicine.medical_treatment Immunology Inflammation Blood Sedimentation Polymorphism Single Nucleotide Severity of Illness Index Gastroenterology Cohort Studies Rheumatology Predictive Value of Tests Internal medicine medicine Humans Immunology and Allergy Spondylitis Ankylosing Longitudinal Studies Promoter Regions Genetic Alleles Ankylosing spondylitis medicine.diagnostic_test Tumor Necrosis Factor-alpha business.industry Middle Aged medicine.disease TNF inhibitor Cross-Sectional Studies Phenotype Treatment Outcome Pharmacogenetics Antirheumatic Agents Erythrocyte sedimentation rate Female Tumor necrosis factor alpha medicine.symptom Age of onset business Biomarkers Uveitis |
| Zdroj: | The Journal of Rheumatology. 41:1675-1682 |
| ISSN: | 1499-2752 0315-162X |
| Popis: | Objective.Despite the clinical efficacy of tumor necrosis factor inhibitors (TNFi), the manner in which TNF-α contributes to disease in patients with ankylosing spondylitis (AS) remains unresolved. We investigated the relationship between TNF-α gene promoter region polymorphism, serum TNF-α levels, and clinical phenotype.Methods.We did a cross-sectional and longitudinal cohort study in TNFi-naive patients with AS (n = 335). Clinical data and biological samples were collected during a research visit with genotyping for TNF-α −238 A/G and −308 A/G performed by Taqman RT-PCR and TNF levels determined by sandwich ELISA. Longitudinal TNF levels were monitored in unselected patients (n = 61).Results.TNF-α −308 GA/AA genotype was present in 14% and TNF-α −238 GA/AA genotype in 1% of patients. TNF-α −308 GA/AA genotype was associated with a reduced risk of uveitis and better spinal function, while TNF-α −238 GA/AA genotype was associated with later age of onset and lower erythrocyte sedimentation rate (ESR). Serum TNF-α level was lower in patients with AS (151 pg/ml) than in controls (263 pg/ml), because more patients with AS had undetectable serum TNF-α (66 vs 25%, p < 0.001). TNFi treatment did not influence serum TNF-α. There was no effect of TNF-α −308/−238 or HLA-B27 genotype on serum TNF-α or subsequent initiation of TNFi.Conclusion.TNF-α −238 or −308 GA/AA genotypes in patients with AS are associated with signs of less severe disease. Serum TNF-α is, however, undetectable in two-thirds of patients with AS and is not influenced by TNF-α promoter genotype or TNFi therapy. These data suggest a more significant role for TNF-α at local sites of inflammation in AS than through systemic effects. |
| Databáze: | OpenAIRE |
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