Influence of DEFB4 copy number variants on gene expression in monocytes

Beta-defensins, a group of antimicrobial peptides that can modulate immune response, are encoded by genes (DEFBs) on chromosome 8p23.1, a region subject to copy number variations (CNVs). This study aimed to investigate the influence of DEFB4 CNV on both mRNA and protein expression in human monocytes.

A cohort of 862 healthy blood donors was screened for DEFB4 copy number (CN) by paralog ratio test and 66 individuals were recalled for a second blood donation. Monocytes were isolated from peripheral blood and stimulated by LPS. DEFB4 mRNA and β-defensin 2 protein levels were quantified using qPCR and ELISA, respectively. DEFB4 CN was precisely determined via ddPCR. DEFB4 mRNA was undetectable in unstimulated monocytes but inducible by LPS. Beta-defensin 2 was detectable in freshly isolated monocytes. After stimulation with LPS, beta-defensin 2 was strongly induced and the level was significantly higher than that of non-stimulated controls. A significant correlation between DEFB4 CN and mRNA expression level was found (P < 0.05, r_s = 0.25). However, no correlation between DEFB4 CN and protein expression including baseline level and the level after stimulation was found (P > 0.05). In conclusion, DEFB4 CNV has an impact on gene expression in mRNA but not protein level in monocytes.