Resumen de The ?2-adrenoreceptor gene promoter polymorphisms may modulate ?2-agonist- and glucocorticoid-induced IgE synthesis
M. Chalubinski, J. Grzegorczyk, M. Jarzebska, M L. Kowalski
Background ?2-adrenoreceptor (?2-AR) agonists and glucocorticoids (GCS) were shown to induce IgE synthesis in human PBMCs. Serum total IgE levels are associated with single nucleotide polymorphisms (SNPs) of the ?2-AR gene. We aimed to assess the association of the effect of fenoterol (?2-AR agonist) on IL-4-driven and budesonide-induced IgE synthesis with genetic variants of ?2-AR.
Methods The study included 25 individuals: 13 with allergic asthma and/or allergic rhinitis and 12 healthy volunteers. PBMCs were cultured with IL-4, fenoterol and/or budesonide, and IgE concentrations in supernatants were assessed. Five SNPs in positions: -47, -20, 46, 79 and 252 of ?2-AR were determined by direct DNA sequencing.
Results In -47 T/T and -20 T/T patients, incubation with fenoterol resulted in decreased IgE production, whereas in -47 C/T and -47 C/C as well as in -20 C/T and -20 C/C individuals, it was enhanced. In contrast to fenoterol, budesonide-induced IgE synthesis was significantly increased in -47 T/T and -20 T/T patients as compared to -47 C/T, -47 C/C, -20 C/T and -47 C/C individuals. Polymorphisms in positions 46, 79 and 252 were not associated with fenoterol- or budesonide-modulated IgE synthesis. No differences in the distribution of IgE synthesis was seen between atopic and non-atopic individuals carrying the same alleles.
Conclusions The differential effect of ?2-agonists and GCS on IgE synthesis may be associated with genetic variants of promoter region of the ?2-AR gene.
