title: Atopic dermatitis is associated with a functional mutation in the promoter of the C-C chemokine RANTES.
abstract: 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.
authors.affiliation: Division of Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Nickel
authors.forename: V
authors.initials: V
authors.lastname: Casolaro
authors.forename: U
authors.initials: U
authors.lastname: Wahn
authors.forename: K
authors.initials: K
authors.lastname: Beyer
authors.forename: K C
authors.initials: KC
authors.lastname: Barnes
authors.forename: B S
authors.initials: BS
authors.lastname: Plunkett
authors.forename: L R
authors.initials: LR
authors.lastname: Freidhoff
authors.forename: C
authors.initials: C
authors.lastname: Sengler
authors.forename: J R
authors.initials: JR
authors.lastname: Plitt
authors.forename: R P
authors.initials: RP
authors.lastname: Schleimer
authors.forename: L
authors.initials: L
authors.lastname: Caraballo
authors.forename: R P
authors.initials: RP
authors.lastname: Naidu
authors.forename: P N
authors.initials: PN
authors.lastname: Levett
authors.forename: T H
authors.initials: TH
authors.lastname: Beaty
authors.forename: S K
authors.initials: SK
authors.lastname: Huang
mesh_terms: D000483:Alleles; D018946:Chemokine CCL5 / Q000235:genetics*; D004252:DNA Mutational Analysis; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology*; D005787:Gene Frequency / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D009154:Mutation / Q000276:immunology*; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D018946:Chemokine CCL5