Interleukin-6 receptor polymorphism is prevalent in HIV-negative Castleman Disease and is associated with increased soluble interleukin-6 receptor levels

PLoS One. 2013;8(1):e54610. doi: 10.1371/journal.pone.0054610. Epub 2013 Jan 23.

Abstract

Multicentric Castleman Disease is largely driven by increased signaling in the pathway for the plasma cell growth factor interleukin-6. We hypothesized that interleukin-6/interleukin-6 receptor/gp130 polymorphisms contribute to increased interleukin-6 and/or other components of the interleukin-6 signaling pathway in HIV-negative Castleman Disease patients. The study group was composed of 58 patients and 50 healthy donors of a similar racial/ethnic profile. Of seven polymorphisms chosen for analysis, we observed an increased frequency between patients and controls of the minor allele of interleukin-6 receptor polymorphism rs4537545, which is in linkage disequilibrium with interleukin-6 receptor polymorphism rs2228145. Further, individuals possessing at least one copy of the minor allele of either polymorphism expressed higher levels of soluble interleukin-6 receptor. These elevated interleukin-6 receptor levels may contribute to increased interleukin-6 activity through the trans-signaling pathway. These data suggest that interleukin-6 receptor polymorphism may be a contributing factor in Castleman Disease, and further research is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Castleman Disease / genetics*
  • Castleman Disease / metabolism*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Male
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin-6 / genetics*
  • Receptors, Interleukin-6 / metabolism*

Substances

  • Interleukin-6
  • Receptors, Interleukin-6

Grant support

This work was supported by Janssen Research and Development, a Johnson and Johnson Company. The funders developed the panoptic interleukin-6 assay and performed this testing. The funders had no role in study design, decision to publish, or preparation of the manuscript.