Polymorphisms in the FcεRIβ Promoter Region Affecting Transcription Activity: A Possible Promoter-Dependent Mechanism for Association between FcεRIβ and Atopy

The β subunit of the high-affinity IgE receptor (FceRI) plays an important role in IgE-mediated allergic reactions as an amplifier for cell surface expression and signal transduction of FceRI. FceRI β is presumed to be one of the genes linked with atopic diseases. However, the validity of the associations previously found between single nucleotide polymorphisms (SNPs) in FceRI β and atopic diseases is questionable. In the present study, we found correlation between the SNP of FceRI β at +6960A/G, resulting in a Glu237Gly amino acid substitution, and the cell surface expression level of FceRI on blood basophils, although it has been shown that the Glu237Gly mutation itself does not affect the surface expression or function of FceRI. We additionally found four SNPs in the promoter region of FceRI β, among which −426T/C and −654C/T were tightly linked with +6960A/G. Reporter plasmids carrying the −426C and −654T promoter displayed higher transcriptional activity than those carrying the −426T and −654C promoter. We found that transcription factor YY1 preferentially bound and transactivated the −654T promoter. Furthermore, expression of FceRI β-chain mRNA in basophils from individuals who have the minor heterozygous genotype was significantly higher than that of the major homozygous genotype. These results suggest that the SNPs in the FceRI β promoter are causally linked with atopy via regulation of FceRI expression.