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

S. Rafiq, K. Stevens, A. J. Hurst, A. Murray, W. Henley, M. N. Weedon, S. Bandinelli, A. M. Corsi, J. M. Guralnik, L. Ferruci, D. Melzer, T. M. Frayling

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)344-351
Number of pages8
JournalGenes and Immunity
Volume8
Issue number4
DOIs
StatePublished - Jun 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Fingerprint

Dive into the research topics of 'Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels'. Together they form a unique fingerprint.

Cite this