IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: interaction with their plasma levels
| Autor: | Pierre Miossec, T Silvestri, N. Buchs, Edouard Vannier, Gordon W. Duff, F. S. Di Giovine |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Sialoglycoproteins Immunology Arthritis Biology Gastroenterology Severity of Illness Index Pathogenesis Arthritis Rheumatoid Internal medicine Genetics medicine Humans Allele Genetics (clinical) Genetic association DNA Primers Polymorphism Genetic medicine.diagnostic_test Base Sequence medicine.disease Receptor antagonist Interleukin 1 Receptor Antagonist Protein Rheumatoid arthritis Erythrocyte sedimentation rate Gene polymorphism Interleukin-1 |
| Zdroj: | Genes and immunity. 2(4) |
| ISSN: | 1466-4879 |
| Popis: | The balance between interleukin-1 (IL-1) and its competitive antagonist IL-1 receptor antagonist (IL-1Ra) may contribute to the pathogenesis of rheumatoid arthritis (RA). We analysed the frequency of different alleles in the IL-1B gene (at -511 and at +3954) as well as in the IL-1Ra gene (at +2018) in an association study involving 297 RA patients and 112 healthy controls from the same geographic area. We tested associations with RA susceptibility or severity, and with circulating levels of IL-1Ra and IL-1b. Carriage of the rare IL-1B (+3954) allele 2 was increased in destructive arthritis (DRA) as compared to non-destructive arthritis (NDRA) (OR 1.7, 95% CI 1.1‐2.8, 49.0% vs 35.9%) and controls (OR 1.7, 95% CI 1.1‐2.8, 35.8%). Patients carrying this allele had a more destructive (Larsen wrist radiological index: mean ∠ s.e.m., 2.1 ∠ 0.2 vs 1.6 ∠ 0.1, P = 0.005; Steinbrocker functional index: 2.4 ∠ 0.1 vs 1.9 ∠ 0.1, P = 0.002) and active disease (Ritchie articular index: 8.1 ∠ 0.8 vs 5.3 ∠ 0.6, P = 0.002; erythrocyte sedimentation rate (ESR): 36.6 ∠ 2.9 mm/h vs 25.3 ∠ 1.8 mm/h, P = 0.002). This contribution was independent from that of HLA DR4/DR1 to severity. IL-1Ra plasma levels adjusted to ESR values were significantly lower in IL-1B2 (3954) positive than negative RA patients (1.0 ∠ 0.1 vs 1.2 ∠ 0.1 ng/ml, P = 0.01). This IL-1B (+3954) gene polymorphism may be an important marker for the severity of joint destruction in RA and is associated with an imbalance in IL-1Ra production. As this genetic association was independent and additive to the risk of HLA DR4/DR1 status, it could be a useful addition to HLA-DR4/1 as a genetic prognostic marker early in the course of the disease. Genes and Immunity (2001) 2, 222‐228. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|