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RI
-Chain Promoter Affecting the Transcription Activity: Possible Relationship to Allergic Diseases1






* Atopy (Allergy) Research Center, and Departments of
Dermatology and
Immunology, Juntendo University School of Medicine, Tokyo, Japan;
Department of Pediatrics, Yamaguchi University School of Medicine, Yamaguchi, Japan;
¶
Biotechnology Research Center, University of Tokyo, Tokyo, Japan; and
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Department of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan
We found a novel polymorphism, -66T/C, in the promoter region of human Fc
RI
, the specific component of the high affinity receptor for IgE (Fc
RI), which is essential for the cell surface expression of Fc
RI and the binding of IgE Ab. When the effect of the single nucleotide replacement on the promoter function was analyzed, the transcription activity of the T allele promoter was found to be higher than that of the C allele promoter, and was markedly up-regulated by the overexpression of GATA-1 when compared with the C allele promoter. This is probably because the promoter with T at -66 has an additional GATA-1-binding motif in the region, which may assure higher affinity of the transcription factor to the promoter. In accordance with this, EMSA actually indicated that GATA-1 bound to the T allele probe (-80/-59) with the affinity higher than that to the C allele probe. Statistical analysis suggested that a significant portion of nonallergic individuals has heterozygous -66T/C genotype, while most of allergic individuals have homozygous -66T/T genotype in Japanese population. Our findings for the first time demonstrate the presence of Fc
RI
polymorphism related to the allergic diseases.
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