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IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: interaction with their plasma levels

Genes & Immunity volume 2, pages 222–228 (2001)Cite this article

Abstract

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-1β. 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.

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Authors and Affiliations

  1. Departments of Immunology and Rheumatology, Hôpital Edouard Herriot, Lyon, France

    N Buchs & P Miossec

  2. Division of Genomic Medicine, University of Sheffield, UK

    FS di Giovine, T Silvestri & GW Duff

  3. Department of Medicine, Tufts University and New England Medical Center, Boston, MA, USA

    E Vannier

Authors
  1. N Buchs
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  2. FS di Giovine
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  3. T Silvestri
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  4. E Vannier
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  5. GW Duff
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  6. P Miossec
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Correspondence to P Miossec.

Additional information

These studies have been supported in part by grants from the Hospices Civils de Lyon, the European Union (Biomed-2 program contract BMH4-CT96-1698), the Association de Recherche sur la Polyarthrite (ARP) and the Arthritis Research Campaign for UK (ARC). Nicolas Buchs was supported by a fellowship from the Swiss National Science Foundation.

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Buchs, N., di Giovine, F., Silvestri, T. et al. IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: interaction with their plasma levels . Genes Immun 2, 222–228 (2001). https://doi.org/10.1038/sj.gene.6363766

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