The α-chain of high-affinity receptor for IgE (FcεRIα) gene polymorphisms and serum IgE levels

Background: The high-affinity receptor for immunoglobulin-E (IgE) (Fc epsilon RI) plays a major role in the pathogenesis of allergy, but there are only two published studies on its alpha subunit (Fc epsilon RI alpha) genetic variability in allergic diseases. Aims of the Study: Mutational screening in the region of the Fc epsilon RI alpha gene promoter and the first exon with subsequent genetic variability assessment in allergic patients and a random population sample. Methods: Allergic subjects were individuals with asthma or urticaria. Age- and sex-matched controls were randomly selected from a large population sample. Mutational screening was performed using a single-stranded conformational polymorphism and subsequent sequencing. Detected polymorphisms were genotyped by restriction fragment length polymorphism. Total serum IgE was measured in allergic subjects and controls. Skin prick tests, blood eosinophil count and aspirin challenge test were performed only in the subjects. A subgroup of the subjects was further characterized by autologous serum skin test, histamine release test, Phadiatop and IgE antibodies against staphylococcal enterotoxins. Results: Two linked polymorphisms -344 C > T and -95 T > C were found within the Fc epsilon RI alpha gene. The allele -344 T frequency was 0.45 vs 0.37 (P = 0.33), and the allele -95 C frequency was 0.26 in subjects vs 0.30 in controls (P = 0.62). Serum IgE was significantly higher in subjects homozygous for the -344T allele (TT genotype) than in those carrying the -344 C allele (CT or CC genotype; P = 0.003), but this association was not detectable in controls. Conclusions: Our findings of genotype-related differences in IgE levels in allergic patients suggest an impact of -344 C > T but not -95 T > C gene polymorphism of Fc epsilon RI alpha on total levels of IgE. The genetic variability in Fc epsilon RI alpha at the -344 nucleotide of its regulatory sequence, though not related to atopy, predicts higher levels of the immunoglobulin.