Enhanced fMLP-stimulated chemotaxis in human neutrophils from individuals carrying the G protein beta3 subunit 825 T-allele.

We have recently described a C825T polymorphism in the gene encoding for the Gbeta3 subunit of heterotrimeric G proteins. The 825T allele is associated with a novel splice variant (Gbeta3-s) and enhanced signal transduction via pertussis toxin (PTX)-sensitive G proteins. fMLP-induced chemotaxis, but not O2- generation, was increased in neutrophils with the TC/TT (EC50 = 1.5 +/- 1.3 nM) genotypes compared to the CC genotype (EC50 = 5.9 +/- 1.5 nM). Maximal fMLP-induced increase in [Ca2+]i was significantly reduced in neutrophils from individuals with TC/TT genotype vs. CC genotype (212.9 +/- 10.1 nM vs. 146.4 +/- 24.2 nM). Gbeta3-s appears to be associated with enhanced immune cell function in humans.