Atopic dermatitis is associated with a functional mutation in the promoter of the C-C chemokine RANTES

Renate G. Nickel, Vincenzo Casolaro, Ulrich Wahn, Kirsten Beyer, Kathleen C. Barnes, Beverly S. Plunkett, Linda R. Freidhoff, Claudia Sengler, James R. Plitt, Robert P. Schleimer, Luis Caraballo, Raana P. Naidu, Paul N. Levett, Terri H. Beaty, Shau Ku Huang

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256 引文 斯高帕斯(Scopus)

摘要

Up-regulation of C-C chemokine expression characterizes allergic inflammation and atopic diseases. A functional mutation in the proximal promoter of the RANTES gene has been identified, which results in a new consensus binding site for the GATA transcription factor family. A higher frequency of this allele was observed in individuals of African descent compared with Caucasian subjects (p < 0.00001). The mutant allele was associated with atopic dermatitis in children of the German Multicenter Allergy Study (MAS-90; p < 0.037), but not with asthma. Transient transfections of the human mast cell line HMC-1 and the T cell line Jurkat with reporter vectors driven by either the mutant or wild-type RANTES promoter showed an up to 8-fold higher constitutive transcriptional activity of the mutant promoter. This is the first report to our knowledge of a functional mutation in a chemokine gene promoter. Our findings suggest that the mutation contributes to the development of atopic dermatitis. Its potential role in other inflammatory and infectious disorders, particularly among individuals of African ancestry, remains to be determined.

原文英語
頁(從 - 到)1612-1616
頁數5
期刊Journal of Immunology
164
發行號3
DOIs
出版狀態已發佈 - 二月 1 2000
對外發佈Yes

ASJC Scopus subject areas

  • Immunology

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