A novel -66T/C polymorphism in Fc epsilon RI alpha-chain promoter affecting the transcription activity: possible relationship to allergic diseases.
We found a novel polymorphism, -66T/C, in the promoter region of human FcepsilonRIalpha, the specific component of the high affinity receptor for IgE (FcepsilonRI), which is essential for the cell surface expression of FcepsilonRI 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 FcepsilonRIalpha polymorphism related to the allergic diseases.
Hasegawa
Masanari
M
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Nishiyama
Chiharu
C
Nishiyama
Makoto
M
Akizawa
Yushiro
Y
Mitsuishi
Kouichi
K
Ito
Tomonobu
T
Kawada
Hiroshi
H
Furukawa
Susumu
S
Ra
Chisei
C
Okumura
Ko
K
Ogawa
Hideoki
H
D000818:Animals; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003596:Cytosine; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D005786:Gene Expression Regulation / Q000276:immunology; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D011110:Polymorphism, Genetic / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D021122:Protein Subunits / Q000096:biosynthesis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000096:biosynthesis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology; D013941:Thymine; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C494689:Gata1 protein, mouse; C494690:Gata1 protein, rat; D021122:Protein Subunits; D017455:Receptors, IgE; D014157:Transcription Factors; D003596:Cytosine; D013941:Thymine