Two different transcription factors discriminate the -315C>T polymorphism of the FcεRIα gene:: Binding of Sp1 to -315C and of a high mobility group-related molecule to -315T

The a-chain is a specific component of Fc epsilon RI, which is essential for the cell surface expression of Fc epsilon RI and the binding of IgE. Recently, two single nucleotide polymorphisms (SNPs) in the alpha-chain promoter, -315C>T and -66T>C, have been shown by statistic studies to associate with allergic diseases. The effect of -66 SNP on GATA-1-mediated promoter activity has been already indicated. In the present study, to investigate roles of the -315 SNP on the a-chain promoter functions, the transcription activity was evaluated by reporter assay. The alpha-chain promoter carrying -315T (minor allele) possessed significantly higher transcriptional activity than that of -315C (major allele). EMSA indicated that the transcription factor Sp1, but not Myc-associated zinc finger protein (MAZ), was bound to the -315C allele probe and that a transcription factor belonging to a high mobility group-family bound to the -315T allele probe. The chromatin immunoprecipitation assay suggested that high mobility group 1, 2, and Sp1 bound around -315 of Fc epsilon RI alpha genomic DNA in vivo in the human basophil cell line KU812 with -315C/T and in human peripheral blood basophils with -315C/C, respectively. When cell surface expression level of Fc epsilon RI on basophils was analyzed by flow cytometry, basophils from individuals carrying -315T allele expressed significantly higher amount of Fc epsilon RI compared with those of -315C/C. The findings demonstrate that a -315 SNP significantly affects human Fc epsilon RI alpha-chain promoter activity and expression level of FcERI on basophils by binding different transcription factors to the SNP site.