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Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels

Genes & Immunity volume 8, pages 344–351 (2007)Cite this article

Abstract

Interleukin-1-receptor antagonist (IL-1RA) modulates the biological activity of the proinflammatory cytokine interleukin-1 (IL-1) and could play an important role in the pathophysiology of inflammatory and metabolic traits. We genotyped seven single nucleotide polymorphisms (SNPs) that capture a large proportion of common genetic variation in the IL-1RN gene in 1256 participants from the Invecchiare in Chianti study. We identified five SNPs associated with circulating IL-1RA levels with varying degrees of significance (P-value range=0.016–4.9 × 10−5). We showed that this association is likely to be driven by one haplotype, most strongly tagged by rs4251961. This variant is only in weak linkage disequilibrium (r2=0.25) with a previously reported variable number of tandem repeats polymorphism (VNTR) in intron-2 although a second variant, rs579543, that tags the VNTR (r2=0.91), may also be independently associated with IL-1RA levels (P=0.03). We found suggestive evidence that the C allele at rs4251961 that lowers IL-1RA levels is associated with an increased IL-1β (P=0.03) level and may also be associated with interferon -γ (P=0.03), α-2 macroglobulin (P=0.008) and adiponectin (P=0.007) serum levels. In conclusion, common variation across the IL-1RN gene is strongly associated with IL-1RA levels.

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Acknowledgements

This work was supported in part by the National Institutes of Health/National Institute on Aging grant R01 AG24233-01 and by the Intramural Research Program, National Institute on Aging, NIH. DM is supported by a National Health Service (NHS) Executive National Public Health Career Scientist Awards, Ref: PHCSA/00/002.

The InCHIANTI study was supported as a ‘targeted project’ (ICS 110.1RS97.71) by the Italian Ministry of Health, by the US National Institute on Aging (contracts N01-AG-916413, N01-AG-821336 and contracts 263 MD 9164 13 and 263 MD 821336). Michael N Weedon is a Vandervell Foundation Research Fellow.

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Authors and Affiliations

  1. Peninsula College of Medicine and Dentistry, Exeter, UK

    S Rafiq, K Stevens, A J Hurst, A Murray, M N Weedon, D Melzer & T M Frayling

  2. School of Mathematics and Statistics, University of Plymouth, Plymouth, UK

    W Henley

  3. Laboratory of Clinical Epidemiology, Italian National Research Council on Aging, Geriatric Rehabilitation Unit, ASF, Florence, Italy

    S Bandinelli

  4. Tuscany Regional Health Agency, I.O.T, Florence, Italy

    A M Corsi

  5. Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy

    A M Corsi

  6. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD, USA

    J M Guralnik

  7. Longitudinal Studies Section, Clinical Research Branch, Gerontology Research Center, National Institute on Aging, Baltimore, MD, USA

    L Ferruci

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Correspondence to T M Frayling.

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Rafiq, S., Stevens, K., Hurst, A. et al. Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels. Genes Immun 8, 344–351 (2007). https://doi.org/10.1038/sj.gene.6364393

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