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The Journal of Immunology, 2003, 171: 1927-1933.
Copyright © 2003 by The American Association of Immunologists

A Novel -66T/C Polymorphism in Fc{epsilon}RI {alpha}-Chain Promoter Affecting the Transcription Activity: Possible Relationship to Allergic Diseases1

Masanari Hasegawa*,§, Chiharu Nishiyama2,*, Makoto Nishiyama, Yushiro Akizawa*, Kouichi Mitsuishi*,{dagger}, Tomonobu Ito*, Hiroshi Kawada*,{dagger}, Susumu Furukawa§, Chisei Ra*,||, Ko Okumura*,{ddagger} and Hideoki Ogawa*,{dagger}

* Atopy (Allergy) Research Center, and Departments of {dagger} Dermatology and {ddagger} 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 || 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{epsilon}RI{alpha}, the specific component of the high affinity receptor for IgE (Fc{epsilon}RI), which is essential for the cell surface expression of Fc{epsilon}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{epsilon}RI{alpha} polymorphism related to the allergic diseases.




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