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

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. (C) 2011 Elsevier B.V. All rights reserved.