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

Up-regulation of C-C chemokine expression characterizes allergic inflammati on and atopic diseases. A functional mutation in the proximal promoter of t he RANTES gene has been identified, which results in a new consensus bindin g site for the GATA transcription factor family. A higher frequency of this allele was observed in individuals of African descent compared with Caucas ian subjects (p < 0.00001), The mutant allele was associated with atopic de rmatitis 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 eithe r the mutant or wild-type RANTES promoter showed an up to 8-fold higher con stitutive transcriptional activity of the mutant promoter. This is the firs t report to our knowledge of a functional mutation in a chemokine gene prom oter, Our findings suggest that the mutation contributes to the development of atopic dermatitis, Its potential role in other inflammatory and infecti ous disorders, particularly among individuals of African ancestry, remains to be determined.