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

Genes Immun. 2007 Oct;8(7):552-9. doi: 10.1038/sj.gene.6364414. Epub 2007 Aug 2.


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 (r(2)=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 x 10(-62). The minor allele of rs4537545 was also associated with higher circulating IL-6 levels (P=1.9 x 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Cytokine Receptor gp130 / blood
  • Cytokines / blood
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Interleukin-6 / blood
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin-6 / blood
  • Receptors, Interleukin-6 / genetics*


  • Cytokines
  • Interleukin-6
  • Receptors, Interleukin-6
  • Cytokine Receptor gp130