A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects

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

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin-6 (IL-6) is a key inflammatory cytokine, signalling to most tissues by binding to a soluble IL-6 receptor (sIL-6r), making a complex with gp130. We used 1273 subjects (mean age 68 years) from the InCHIANTI Italian cohort to study common variation in the IL-6r locus and associations with interleukin 6 receptor (IL-6r), IL-6, gp130 and a battery of inflammatory markers. The rs4537545 single nucleotide polymorphism (SNP) tags the functional non-synonymous Asp358Ala variant (rs8192284) in IL-6r (r2 = 0.89, n = 343). Individuals homozygous for the rs4537545 SNP minor allele (frequency 40%) had a doubling of IL-6r levels (132.48 pg/ml, 95% CI 125.13-140.27) compared to the common allele homozygous group (68.31 pg/ml, 95% CI 65.35-71.41): in per allele regression models, the rs4537545 SNP accounted for 20% of the variance in sIL-6r, with P = 5.1 × 10-62. The minor allele of rs4537545 was also associated with higher circulating IL-6 levels (P = 1.9 × 10-4). There was no association of this variant with serum levels of gp130 or with any of the studied pro- and anti-inflammatory markers. A common variant of the IL-6r gene results in major changes in IL-6r and IL-6 serum levels, but with no apparent effect on gp130 levels or on inflammatory status in the general population.

Original languageEnglish (US)
Pages (from-to)552-559
Number of pages8
JournalGenes and Immunity
Volume8
Issue number7
DOIs
StatePublished - Oct 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

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