Copy number variation of CCL3L1 influences asthma risk by modulating IL-10 expression

Clin Chim Acta. 2011 Nov 20;412(23-24):2100-4. doi: 10.1016/j.cca.2011.07.017. Epub 2011 Jul 26.

Abstract

Background: Copy number of Chemokine ligand 3-like 1 (CCL3L1) is associated with various immune disorders. This study was conducted to assess the role of CCL3L1 in asthma by both association analyses of human subjects and in vitro functional analyses.

Methods: We analyzed the copy number of the CCL3L1 gene in 533 Korean subjects (372 controls and 161 asthma patients) by real-time PCR, and investigated the effect of recombinant CCL3L1 protein on THP-1 human monocytic cells that were stimulated with house dust mite extract.

Results: The mean copy number of CCL3L1 in asthma subjects was significantly lower than that of control subjects (3.18 vs. 3.75, p=0.001). A low copy number of ≤1 was significantly associated with increased asthma risk with an odds ratio of 2.47, and a high copy number of ≥5 was associated with decreased asthma risk with an odds ratio of 0.40. Subjects with ≤1 copy of CCL3L1 had significantly lower mRNA levels of CCL3L1 in peripheral blood cells, and significantly higher serum IgE levels (p<0.05). In the house dust mite extract-simulated THP-1 monocytic cells, CCL3L1 protein dose-dependently up-regulated the expression of IL-10, an anti-inflammatory cytokine.

Conclusion: Copy number of CCL3L1 may influence asthma risk by modulating IL-10 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / genetics*
  • Asthma / immunology
  • Base Sequence
  • Case-Control Studies
  • Cell Line
  • Chemokines, CC / genetics*
  • DNA Copy Number Variations*
  • DNA Primers
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology
  • Interleukin-10 / genetics*
  • Male
  • Middle Aged
  • Real-Time Polymerase Chain Reaction

Substances

  • CCL3L1 protein, human
  • Chemokines, CC
  • DNA Primers
  • Interleukin-10